(3.236.100.86) 您好!臺灣時間:2021/05/06 13:45
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:何協勳
研究生(外文):Hsieh-Hsun
論文名稱:桑椹萃取物抑制低密度脂蛋白氧化,與抑制血管平滑肌細胞轉移及增生作用
論文名稱(外文):Mulberry extracts inhibit LDL oxidation, vascular smoothmuscle cell migration and proliferation.
指導教授:王朝鐘王朝鐘引用關係
指導教授(外文):Chau-Jong Wang
學位類別:博士
校院名稱:中山醫學大學
系所名稱:生化暨生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:418
相關次數:
  • 被引用被引用:0
  • 點閱點閱:159
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
近年來,科學家在追尋抗氧化、抗衰老的過程中,發現在一些高等植物中所含之多酚化合物,具有抗氧化作用,眾多研究證實藉由抗氧化作用可用來抑制LDL的氧化修飾,是一種有效預防動脈粥狀硬化發生的方法。心血管疾病與癌症為現代人生命健康的二大殺手,而心血管疾病中動脈粥狀硬化(Atherosclerosis)是主要的致死原因。而關於動脈粥狀硬化的眾多推論中,1.低密度脂蛋白(LDL)在血管內膜(intima)受到的氧化修飾作用(oxidative modification)、2.動脈平滑肌細胞受血管內膜中發炎因子的刺激而從血管中層 (media) 轉移到血管內膜(intima)及3.血管內膜(intima)動脈平滑肌細胞過度的增生作用,被視為是早期動脈粥狀硬化的一些致病原因。如有天然物質能保護LDL不受氧化修飾影響並能抑制血管平滑肌細胞的增生,則能有效預防動脈粥狀硬化的發生。
第一部分:首先分離桑椹水萃取物(MWEs)及其中所含之多酚化合物(MPEs)探討其抗氧化與抑制泡沫細胞(foam cells)形成的能力。本研究證據顯示桑椹葉與桑椹果粒中含有豐富類黃酮素與酚酸,具有抗氧化作用。從銅離子誘導LDL進行體外氧化實驗的模式中發現,添加桑椹果粒萃取物後,LDL受到氧化修飾所造成的Apo B蛋白斷裂現象及LDL蛋白表面電荷改變的程度明顯降低。而脂質過氧化產物MDA的生成量亦減少,且具有清除1,1-diphenyl-2-picrylhy drazyl(DPPH)自由基的作用;而這樣的現象在多酚萃取物的一組更為明顯,更加確認了這些萃取物具有強的抗氧化能力。除此之外;在本實驗中証實桑椹萃取物能有效抑制巨噬細胞scavenger receptors(CD36、SR-A)的表達,進而達到抑制泡沫細胞的形成。
第二部分:此本研究之目的在於探討桑椹果粒的水萃取物(MWEs)、多酚萃取物(MPEs),誘導血管平滑肌細胞(VSMC)程序性凋亡(apoptosis)的影響、並觀察是否能抑制血管平滑肌細胞轉移到血管內膜(intima)。在細胞實驗方面,發現桑椹萃取物會誘導過度增生狀態的VSMC凋謝死亡(apoptosis)。從western blot的結果顯示:與凋謝死亡相關的蛋白(apoptotic-related proteins)如:p-p53、Myc、Bax、Fas、FasL、cytochrome c、caspase 3,8,9、MAPK family(p-SEK、p38、p-JNK、p-Jun),在桑椹萃取物處理後的細胞中呈現增加的趨勢。相對的抗凋謝死亡的相關蛋白(anti-apoptotic related proteins)Bcl-2、Mcl-1、PI3K、Akt、NF-κB等,表現量則都明顯下降。推測桑椹萃取物主要在於抑制anti-apoptotic related proteins的表達進而誘發細胞產生apoptosis。
第三部分:利用較低的劑量來探討桑椹萃取物對VSMC增生的影響,Flow cytometry分析結果發現,VSMC受萃取物的影響下,細胞週期有停滯於G1 phase的現象。在西方墨點法(Western blotting)的分析方面,phosspho-p53(p-p53)、p27、p21、p16表現皆有增加的情形;透過免疫沉澱法(Immunoprecipitation)分析得知cyclin D1/CDK4、cyclin A、E/CDK2及p53/Mdm2蛋白實際結合情形隨著萃取物處理時間增加而減少。最後證實,桑椹萃取物可藉由iNOS誘導血管平滑肌細胞NO產生並活化AMPK,藉此機轉而誘導VSMC細胞週期停滯。
第四部分:利用不影響生長的劑量觀察桑椹萃取物對於VSMC移動能力的影響;傷口癒合(wound healing assay)、Boyden chamber分析的結果中,都發現明顯抑制的現象,進一步用Zymography assay、western blot、EMSA(Electrophoretic mobility shift assay)分析,證實是桑椹萃取物透過降低NF-κB轉錄活性進而降低Matrix metalloproteinases-2(MMP-2)基因的表現;另外FAK、RhoA、Rac-1、Cdc42、Ras調節細胞移動與細胞骨架組裝的蛋白,其蛋白表現也受到抑制。最後在Ras轉殖的一連串實驗中證實,桑椹萃取物可透過iNOS與AMPK的活化造成Ras蛋白的分解,進而達到抑制VSMC移動的能力。
第五部分:利用Ras轉職誘導VSMC老化的模式中,發現桑椹多酚萃取物能有效抑制老化指標β-Galactosidase的活性,並恢復老化VSMC細胞週期的運行。最後證實桑椹萃取物是透過AMPK活化而抑制VSMC中Ras的過度表現,而達到減緩Ras所誘導的細胞老化。表示桑椹萃取物透過抑制VSMC細胞老化的現象,可以減少血管斑塊不穩定與剝離的機會。
綜合上述結果顯示,桑椹萃取物(MWEs與MPEs)同時兼具抗LDL氧化及抑制血管平滑肌細胞增生的作用、而在極低的劑量下就能成功的預防血管平滑肌細胞的轉移與老化。推測其具有良好保護心臟血管的功能,可作為將來自然保健產品的開發與應用。

Atherosclerosis, a disease occurring in arteries, is one of the primary causes of heart diseases and is often the cause of death. Previous studies have shown that atherosclerosis is closely r elated to oxidative low-density lipoprotein dk3u3d. The oxidative modification hypothesis proposes that low density lipoprotein (LDL) oxidation and foam cell formation. Mulberry, a local edible fruit of Morus alba L., is used effectively in traditional medicines against fever, hepatic damage, rheumatic arthritis and hypertension. But few studies have investigated in detail the mechanism and effects of the mulberry fruit against atherosclerosis. In recent studies, the oxidative modification of LDL plays a key role in the pathogenesis of atherosclerosis. In this study, we evaluated two extracts, MWEs (mulberry water extracts) and MPEs (mulberry polyphenol-rich extracts ), which exhibited antioxidative ability in vitro. The antioxidative activity of the mulberry extracts on LDL oxidation was defined by relative electrophoretic mobility (REM), fragmentation of Apo B, thiobarbituric acid reaction substances (TBARS), and radical scavenging assay. Our results showed that low doses of MPEs were able to reduce the REM, Apo B fragmentation, and MDA formation in Cu2+-mediacted LDL oxidation model. MWEs and MPEs also had strong ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging. Further, we demonstrated that mulberry extracts could inhibit the foam cell formation and inhibit the expression of the macrophages scavenger receptors (CD36, SR-A) expression induced by oxLDL. Mulberry extracts showed strong potency for scavenging radical, and inhibiting the LDL oxidation and foam cell formation.
We have demonstrated that the mulberry water extracts (MWEs) can effectively inhibit LDL oxidation and reduce the development of atherosclerosis in cholesterol-fed rabbits, suggesting that these extracts may prevent atherosclerosis by reducing early atherogenesis. The mechanisms by which mulberry extracts reduce the development of atherosclerosis are not yet fully understood. In these experiments, MWEs and MPEs could inhibit the migration and proliferation of ASMCs (A7r5 cells) by down regulation of Ras/PI3K/Akt pathway. MWEs and MPEs caused cell cycle arrest by inducing AMPK activation and attenuating of cyclin D/CDK and p53/Mdm2 complexes. At highly concentration of the extracts, MWEs and MPEs induced apoptosis by down regulation anti-apoptosis proteins strongly.In conclusion, we not only evaluated the strong antioxidative activity of the polyphenol extracts, but also observed MWEs and MPEs can inhibit proliferation and migration of ASMCs by decreace the transcription activity of NF-κB, FAK, small GTPase, and Ras protein, which were facilitated by integrin receptor. Therefore, it is suggested that the mulberry could be a healthy food to prevent individuals from atherosclerosis .


目錄...................................................1
【壹】、總摘要.........................................3
一、中文摘要.......................................3
二、英文摘要.......................................6
【貳】、研究動機.......................................8
【叁】、實驗藥品與器材.................................9

第一部分:
桑椹萃取物成份分析與抑制泡沫細胞形成之研究........14
壹、緒論..........................................15
貳、研究動機......................................37
叁、研究架構......................................38
肆、實驗方法......................................39
伍、實驗結果......................................58
陸、討論..........................................69
柒、結果圖表......................................73
捌、附圖..........................................83

第二部分:
桑椹萃取物誘發血管平滑肌細胞apoptosis現象.........91
壹、緒論..........................................92
貳、研究動機.....................................102
叁、研究架構.....................................103
肆、實驗方法.....................................104
伍、實驗結果.....................................116
陸、討論.........................................134
柒、結果圖表.....................................139
捌、附圖.........................................183

第三部分:
桑椹萃取物抑制血管平滑肌細胞cell cycle運行之探討.187
壹、緒論.........................................188
貳、研究動機.....................................200
叁、研究架構.....................................201
肆、實驗方法.....................................202
伍、實驗結果.....................................205
陸、討論.........................................213
柒、實驗圖表.....................................215
捌、附圖.........................................231

第四部分:
桑椹萃取物抑制血管平滑肌細胞migration之探討......236
壹、緒論.........................................237
貳、研究動機.....................................251
叁、研究架構.....................................252
肆、實驗方法.....................................254
伍、實驗結果.....................................266
陸、討論.........................................290
柒、結果圖表.....................................295
捌、附圖.........................................336

第五部分:
桑椹萃取物減緩Ras-transfected血管平滑肌細胞的
老化現象.........................................343
壹、緒論.........................................344
貳、研究動機.....................................349
叁、研究架構.....................................350
肆、實驗方法.....................................351
伍、實驗結果.....................................354
陸、討論.........................................362
柒、結果圖表.....................................365
捌、附圖.........................................378

【肆】、總結論.......................................379
【伍】、附圖.........................................387
【陸】、參考文獻.....................................389
【柒】、附錄.........................................418



1.Asano N, Yamashita T, Yasuda K, Ikeda K, Kizu H, Kameda Y, Kato A, Nash RJ, Lee HS, Ryu KS: Polyhydroxylated alkaloids isolated from mulberry trees (Morusalba L.) and silkworms (Bombyx mori L.). J Agric Food Chem 2001, 49(9):4208-4213.
2.Dugo P, Mondello L, Errante G, Zappia G, Dugo G: Identification of anthocyanins in berries by narrow-bore high-performance liquid chromatography with electrospray ionization detection. J Agric Food Chem 2001, 49(8):3987-3992.
3.Mitcheva M, Astroug H, Drenska D, Popov A, Kassarova M: Biochemical and morphological studies on the effects of anthocyans and vitamin E on carbon tetrachloride induced liver injury. Cell Mol Biol (Noisy-le-grand) 1993, 39(4):443-448.
4.Morse MA, Stoner GD: Cancer chemoprevention: principles and prospects. Carcinogenesis 1993, 14(9):1737-1746.
5.Middleton E, Jr., Kandaswami C, Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000, 52(4):673-751.
6.Tewari RK, Kumar P, Sharma PN: Antioxidant responses to enhanced generation of superoxide anion radical and hydrogen peroxide in the copper-stressed mulberry plants. Planta 2006, 223(6):1145-1153.
7.Nattapong S, Omboon L: A new source of whitening agent from a Thai Mulberry plant and its betulinic acid quantitation. Nat Prod Res 2008, 22(9):727-734.
8.Kim AJ, Park S: Mulberry extract supplements ameliorate the inflammation-related hematological parameters in carrageenan-induced arthritic rats. J Med Food 2006, 9(3):431-435.
9.Shih PH, Chan YC, Liao JW, Wang MF, Yen GC: Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry (Morus atropurpurea L.) on senescence-accelerated mice and prevention of Alzheimer''s disease. J Nutr Biochem 2010, 21(7):598-605.
10.Huang HP, Shih YW, Chang YC, Hung CN, Wang CJ: Chemoinhibitory effect of mulberry anthocyanins on melanoma metastasis involved in the Ras/PI3K pathway. J Agric Food Chem 2008, 56(19):9286-9293.
11.Liu LK, Lee HJ, Shih YW, Chyau CC, Wang CJ: Mulberry anthocyanin extracts inhibit LDL oxidation and macrophage-derived foam cell formation induced by oxidative LDL. J Food Sci 2008, 73(6):H113-121.
12.Chen CC, Liu LK, Hsu JD, Huang HP, Y YM, Wang CJ: Mulberry extract inhibits the development of atherosclerosis in cholesterol-fed rabbits Food Chemistry 2005, 91(4):601-607
13.Liu LK, Chou FP, Chen YC, Chyau CC, Ho HH, Wang CJ: Effects of mulberry (Morus alba L.) extracts on lipid homeostasis in vitro and in vivo. J Agric Food Chem 2009, 57(16):7605-7611.
14.鄭雅方: 荷葉多酚活化p38 MAPK/FasL 致人類乳癌細胞MCF-7 凋亡作用. 中山醫學大學生化暨生物科技研究所碩士論文 2006
15.Medina I, Satue-Gracia MT, German JB, Frankel EN: Comparison of natural polyphenol antioxidants from extra virgin olive oil with synthetic antioxidants in tuna lipids during thermal oxidation. J Agric Food Chem 1999, 47(12):4873-4879.
16.Lopes GK, Schulman HM, Hermes-Lima M: Polyphenol tannic acid inhibits hydroxyl radical formation from Fenton reaction by complexing ferrous ions. Biochim Biophys Acta 1999, 1472(1-2):142-152.
17.Bravo L: Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998, 56(11):317-333.
18.Scalbert A, Williamson G: Dietary intake and bioavailability of polyphenols. J Nutr 2000, 130(8S Suppl):2073S-2085S.
19.Sakakibara H, Honda Y, Nakagawa S, Ashida H, Kanazawa K: Simultaneous determination of all polyphenols in vegetables, fruits, and teas. J Agric Food Chem 2003, 51(3):571-581.
20.Scalbert A, Morand C, Manach C, Remesy C: Absorption and metabolism of polyphenols in the gut and impact on health. Biomed Pharmacother 2002, 56(6):276-282.
21.Rice-Evans C: Flavonoid antioxidants. Curr Med Chem 2001, 8(7):797-807.
22.Fuhrman B, Aviram M: Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr Opin Lipidol 2001, 12(1):41-48.
23.Kris-Etherton PM, Keen CL: Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr Opin Lipidol 2002, 13(1):41-49.
24.Herrmann K: Occurrence and content of hydroxycinnamic and hydroxybenzoic acid compounds in foods. Crit Rev Food Sci Nutr 1989, 28(4):315-347.
25.Ness AR, Powles JW: Fruit and vegetables, and cardiovascular disease: a review. Int J Epidemiol 1997, 26(1):1-13.
26.Radtke J, Linseisen J, Wolfram G: [Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey]. Z Ernahrungswiss 1998, 37(2):190-197.
27.Koshihara Y, Neichi T, Murota S, Lao A, Fujimoto Y, Tatsuno T: Caffeic acid is a selective inhibitor for leukotriene biosynthesis. Biochim Biophys Acta 1984, 792(1):92-97.
28.Fernandez MA, Saenz MT, Garcia MD: Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens. J Pharm Pharmacol 1998, 50(10):1183-1186.
29.Gao SW, Chen ZJ: [Effects of sodium ferulate on platelet aggregation and platelet thromboxane A2 in patients with coronary heart disease]. Zhong Xi Yi Jie He Za Zhi 1988, 8(5):263-265, 259.
30.Huang MT, Smart RC, Wong CQ, Conney AH: Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 1988, 48(21):5941-5946.
31.Singh S, Aggarwal BB: Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 1995, 270(42):24995-25000.
32.Laranjinha J, Vierira O, Almeida L, Madeira V: Inhibition of metmyoglobin/H2O2-dependent low density lipoprotein lipid peroxidation by naturally occurring phenolic acids. Biochem Pharmacol 1996, 51(4):395-402.
33.Reddy S, Aggarwal BB: Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. FEBS Lett 1994, 341(1):19-22.
34.Natarajan K, Singh S, Burke TR, Jr., Grunberger D, Aggarwal BB: Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 1996, 93(17):9090-9095.
35.Bito T, Roy S, Sen CK, Packer L: Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radic Biol Med 2000, 28(2):219-227.
36.Duthie G, Crozier A: Plant-derived phenolic antioxidants. Curr Opin Lipidol 2000, 11(1):43-47.
37.Aguilera CM, Ramirez-Tortosa MC, Mesa MD, Gil A: [Protective effect of monounsaturated and polyunsaturated fatty acids on the development of cardiovascular disease]. Nutr Hosp 2001, 16(3):78-91.
38.Bub A, Watzl B, Blockhaus M, Briviba K, Liegibel U, Muller H, Pool-Zobel BL, Rechkemmer G: Fruit juice consumption modulates antioxidative status, immune status and DNA damage. J Nutr Biochem 2003, 14(2):90-98.
39.Yochum L, Kushi LH, Meyer K, Folsom AR: Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol 1999, 149(10):943-949.
40.Hertog MG, Feskens EJ, Kromhout D: Antioxidant flavonols and coronary heart disease risk. Lancet 1997, 349(9053):699.
41.Nigdikar SV, Williams NR, Griffin BA, Howard AN: Consumption of red wine polyphenols reduces the susceptibility of low-density lipoproteins to oxidation in vivo. Am J Clin Nutr 1998, 68(2):258-265.
42.Kuntz S, Wenzel U, Daniel H: Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur J Nutr 1999, 38(3):133-142.
43.Wenzel U, Kuntz S, Brendel MD, Daniel H: Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells. Cancer Res 2000, 60(14):3823-3831.
44.Zhu M, Gong Y, Yang Z, Ge G, Han C, Chen J: Green tea and its major components ameliorate immune dysfunction in mice bearing Lewis lung carcinoma and treated with the carcinogen NNK. Nutr Cancer 1999, 35(1):64-72.
45.Chen PN, Chu SC, Chiou HL, Kuo WH, Chiang CL, Hsieh YS: Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett 2006, 235(2):248-259.
46.Zhang Y, Vareed SK, Nair MG: Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. Life Sci 2005, 76(13):1465-1472.
47.Olsson ME, Gustavsson KE, Andersson S, Nilsson A, Duan RD: Inhibition of cancer cell proliferation in vitro by fruit and berry extracts and correlations with antioxidant levels. J Agric Food Chem 2004, 52(24):7264-7271.
48.Zhao C, Giusti MM, Malik M, Moyer MP, Magnuson BA: Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth. J Agric Food Chem 2004, 52(20):6122-6128.
49.Chen YC, Liang YC, Lin-Shiau SY, Ho CT, Lin JK: Inhibition of TPA-induced protein kinase C and transcription activator protein-1 binding activities by theaflavin-3,3''-digallate from black tea in NIH3T3 cells. J Agric Food Chem 1999, 47(4):1416-1421.
50.Liang YC, Chen YC, Lin YL, Lin-Shiau SY, Ho CT, Lin JK: Suppression of extracellular signals and cell proliferation by the black tea polyphenol, theaflavin-3,3''-digallate. Carcinogenesis 1999, 20(4):733-736.
51.Spencer JP, Abd-el-Mohsen MM, Rice-Evans C: Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity. Arch Biochem Biophys 2004, 423(1):148-161.
52.Ross R: Atherosclerosis--an inflammatory disease. N Engl J Med 1999, 340(2):115-126.
53.Navab M, Berliner JA, Watson AD, Hama SY, Territo MC, Lusis AJ, Shih DM, Van Lenten BJ, Frank JS, Demer LL et al: The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 1996, 16(7):831-842.
54.Caligiuri G, Levy B, Pernow J, Thoren P, Hansson GK: Myocardial infarction mediated by endothelin receptor signaling in hypercholesterolemic mice. Proc Natl Acad Sci U S A 1999, 96(12):6920-6924.
55.Goldstein JL, Brown MS: The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 1977, 46:897-930.
56.Cybulsky MI, Gimbrone MA, Jr.: Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 1991, 251(4995):788-791.
57.Dong ZM, Chapman SM, Brown AA, Frenette PS, Hynes RO, Wagner DD: The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 1998, 102(1):145-152.
58.Collins RG, Velji R, Guevara NV, Hicks MJ, Chan L, Beaudet AL: P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 2000, 191(1):189-194.
59.Han KH, Han KO, Green SR, Quehenberger O: Expression of the monocyte chemoattractant protein-1 receptor CCR2 is increased in hypercholesterolemia. Differential effects of plasma lipoproteins on monocyte function. J Lipid Res 1999, 40(6):1053-1063.
60.Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, Rollins BJ: Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 1998, 2(2):275-281.
61.Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, Young SG, Rollins BJ, Charo IF: MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 1999, 103(6):773-778.
62.Boring L, Gosling J, Cleary M, Charo IF: Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998, 394(6696):894-897.
63.Colles SM, Irwin KC, Chisolm GM: Roles of multiple oxidized LDL lipids in cellular injury: dominance of 7 beta-hydroperoxycholesterol. J Lipid Res 1996, 37(9):2018-2028.
64.Bennett MR, Macdonald K, Chan SW, Boyle JJ, Weissberg PL: Cooperative interactions between RB and p53 regulate cell proliferation, cell senescence, and apoptosis in human vascular smooth muscle cells from atherosclerotic plaques. Circ Res 1998, 82(6):704-712.
65.Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J: Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993, 69(5):377-381.
66.Galis ZS, Sukhova GK, Lark MW, Libby P: Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994, 94(6):2493-2503.
67.Carmeliet P: Proteinases in cardiovascular aneurysms and rupture: targets for therapy? J Clin Invest 2000, 105(11):1519-1520.
68.Vaux DL, Korsmeyer SJ: Cell death in development. Cell 1999, 96(2):245-254.
69.Bennett MR: Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture. Cardiovasc Res 1999, 41(2):361-368.
70.Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL: Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989, 320(14):915-924.
71.Yamada Y, Doi T, Hamakubo T, Kodama T: Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system. Cell Mol Life Sci 1998, 54(7):628-640.
72.Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM: PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998, 93(2):241-252.
73.Jha P, Flather M, Lonn E, Farkouh M, Yusuf S: The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med 1995, 123(11):860-872.
74.Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000, 342(3):154-160.
75.Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Ueda O, Sakaguchi H, Higashi T, Suzuki T et al: A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 1997, 386(6622):292-296.
76.Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF, Sharma K, Silverstein RL: Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 2000, 105(8):1049-1056.
77.Lewis TS, Shapiro PS, Ahn NG: Signal transduction through MAP kinase cascades. Adv Cancer Res 1998, 74:49-139.
78.Cobb MH, Goldsmith EJ: How MAP kinases are regulated. J Biol Chem 1995, 270(25):14843-14846.
79.Lieu CH, Liu CC, Yu TH, Chen KD, Chang YN, Lai YK: Role of mitogen-activated protein kinase in taxol-induced apoptosis in human leukemic U937 cells. Cell Growth Differ 1998, 9(9):767-776.
80.Chang L, Karin M: Mammalian MAP kinase signalling cascades. Nature 2001, 410(6824):37-40.
81.Mohit AA, Martin JH, Miller CA: p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system. Neuron 1995, 14(1):67-78.
82.Ichijo H: From receptors to stress-activated MAP kinases. Oncogene 1999, 18(45):6087-6093.
83.Stadheim TA, Kucera GL: Extracellular signal-regulated kinase (ERK) activity is required for TPA-mediated inhibition of drug-induced apoptosis. Biochem Biophys Res Commun 1998, 245(1):266-271.
84.Ricci R, Sumara G, Sumara I, Rozenberg I, Kurrer M, Akhmedov A, Hersberger M, Eriksson U, Eberli FR, Becher B et al: Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis. Science 2004, 306(5701):1558-1561.
85.Rahaman SO, Lennon DJ, Febbraio M, Podrez EA, Hazen SL, Silverstein RL: A CD36-dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metab 2006, 4(3):211-221.
86.Osman N, Ballinger ML, Dadlani HM, Getachew R, Burch ML, Little PJ: p38 MAP kinase mediated proteoglycan synthesis as a target for the prevention of atherosclerosis. Cardiovasc Hematol Disord Drug Targets 2008, 8(4):287-292.
87.F. See AK, H. Krum: p38 MAP kinase as a therapeutic target in cardiovascular disease Drug Discovery Today: Therapeutic Strategies 2004, 1(2):149-154.
88.Zhao M, Liu Y, Wang X, New L, Han J, Brunk UT: Activation of the p38 MAP kinase pathway is required for foam cell formation from macrophages exposed to oxidized LDL. APMIS 2002, 110(6):458-468.
89.Lei ZB, Zhang Z, Jing Q, Qin YW, Pei G, Cao BZ, Li XY: OxLDL upregulates CXCR2 expression in monocytes via scavenger receptors and activation of p38 mitogen-activated protein kinase. Cardiovasc Res 2002, 53(2):524-532.
90.Jin JO, Park HY, Xu Q, Park JI, Zvyagintseva T, Stonik VA, Kwak JY: Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-alpha. Blood 2009, 113(23):5839-5847.
91.Tabata T, Mine S, Kawahara C, Okada Y, Tanaka Y: Monocyte chemoattractant protein-1 induces scavenger receptor expression and monocyte differentiation into foam cells. Biochem Biophys Res Commun 2003, 305(2):380-385.
92.Yano M, Matsumura T, Senokuchi T, Ishii N, Murata Y, Taketa K, Motoshima H, Taguchi T, Sonoda K, Kukidome D et al: Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages. Circ Res 2007, 100(10):1442-1451.
93.Eguchi A, Murakami A, Ohigashi H: Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells. FEBS Lett 2006, 580(13):3321-3328.
94.Dubois M, Gilles K, Hamilton JK, Rebers PA, Smith F: A colorimetric method for the determination of sugars. Nature 1951, 168(4265):167.
95.Havel RJ, Eder HA, Bragdon JH: The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 1955, 34(9):1345-1353.
96.Reid VC, Mitchinson MJ, Skepper JN: Cytotoxicity of oxidized low-density lipoprotein to mouse peritoneal macrophages: an ultrastructural study. J Pathol 1993, 171(4):321-328.
97.Miura Y, Chiba T, Miura S, Tomita I, Umegaki K, Ikeda M, Tomita T: Green tea polyphenols (flavan 3-ols) prevent oxidative modification of low density lipoproteins: an ex vivo study in humans. J Nutr Biochem 2000, 11(4):216-222.
98.Yagi K, Komura S: Inhibitory effect of female hormones on lipid peroxidation. Biochem Int 1986, 13(6):1051-1055.
99.Ursini F, Maiorino M, Morazzoni P, Roveri A, Pifferi G: A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med 1994, 16(5):547-553.
100.Hsu HY, Twu YC: Tumor necrosis factor-alpha -mediated protein kinases in regulation of scavenger receptor and foam cell formation on macrophage. J Biol Chem 2000, 275(52):41035-41048.
101.Chen JH, Tseng TH, Ho YC, Lin HH, Lin WL, Wang CJ: Gaseous nitrogen oxides stimulate cell cycle progression by retinoblastoma phosphorylation via activation of cyclins/Cdks [correction]. Toxicol Sci 2003, 76(1):83-90.
102.Datta SR, Brunet A, Greenberg ME: Cellular survival: a play in three Akts. Genes Dev 1999, 13(22):2905-2927.
103.Kang JH, Kim JK, Park WH, Park KK, Lee TS, Magae J, Nakajima H, Kim CH, Chang YC: Ascochlorin suppresses oxLDL-induced MMP-9 expression by inhibiting the MEK/ERK signaling pathway in human THP-1 macrophages. J Cell Biochem 2007, 102(2):506-514.
104.Liu WH, Chen XM, Fu B: Thrombin stimulates MMP-9 mRNA expression through AP-1 pathway in human mesangial cells. Acta Pharmacol Sin 2000, 21(7):641-645.
105.Li MH, Jang JH, Surh YJ: Nitric oxide induces apoptosis via AP-1-driven upregulation of COX-2 in rat pheochromocytoma cells. Free Radic Biol Med 2005, 39(7):890-899.
106.Kriehuber E, Bauer W, Charbonnier AS, Winter D, Amatschek S, Tamandl D, Schweifer N, Stingl G, Maurer D: Balance between NF-kappaB and JNK/AP-1 activity controls dendritic cell life and death. Blood 2005, 106(1):175-183.
107.Kerr JF, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972, 26(4):239-257.
108.Van Cruchten S, Van Den Broeck W: Morphological and biochemical aspects of apoptosis, oncosis and necrosis. Anat Histol Embryol 2002, 31(4):214-223.
109.Evan G, Littlewood T: A matter of life and cell death. Science 1998, 281(5381):1317-1322.
110.Buschmann T, Potapova O, Bar-Shira A, Ivanov VN, Fuchs SY, Henderson S, Fried VA, Minamoto T, Alarcon-Vargas D, Pincus MR et al: Jun NH2-terminal kinase phosphorylation of p53 on Thr-81 is important for p53 stabilization and transcriptional activities in response to stress. Mol Cell Biol 2001, 21(8):2743-2754.
111.Hugon J, Esclaire F, Terro F, Yardin C: [Apoptosis and Alzheimer disease. Contribution of cellular and transgenic models]. Rev Neurol (Paris) 2000, 156(2):123-125.
112.Sakahira H, Enari M, Nagata S: Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 1998, 391(6662):96-99.
113.Nagata S: Apoptosis regulated by a death factor and its receptor: Fas ligand and Fas. Philos Trans R Soc Lond B Biol Sci 1994, 345(1313):281-287.
114.Rodriguez J, Lazebnik Y: Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 1999, 13(24):3179-3184.
115.Nagata S: Apoptosis mediated by the Fas system. Prog Mol Subcell Biol 1996, 16:87-103.
116.Fridman JS, Lowe SW: Control of apoptosis by p53. Oncogene 2003, 22(56):9030-9040.
117.Kawahara A, Kobayashi T, Nagata S: Inhibition of Fas-induced apoptosis by Bcl-2. Oncogene 1998, 17(20):2549-2554.
118.Nagata M, Nakauchi H, Nakayama K, Loh D, Watanabe T: Apoptosis during an early stage of nephrogenesis induces renal hypoplasia in bcl-2-deficient mice. Am J Pathol 1996, 148(5):1601-1611.
119.Nagata S, Golstein P: The Fas death factor. Science 1995, 267(5203):1449-1456.
120.Thompson EB: The many roles of c-Myc in apoptosis. Annu Rev Physiol 1998, 60:575-600.
121.Ayer DE, Kretzner L, Eisenman RN: Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell 1993, 72(2):211-222.
122.Packham G, Cleveland JL: The role of ornithine decarboxylase in c-Myc-induced apoptosis. Curr Top Microbiol Immunol 1995, 194:283-290.
123.Dang CV, Resar LM, Emison E, Kim S, Li Q, Prescott JE, Wonsey D, Zeller K: Function of the c-Myc oncogenic transcription factor. Exp Cell Res 1999, 253(1):63-77.
124.Facchini LM, Penn LZ: The molecular role of Myc in growth and transformation: recent discoveries lead to new insights. FASEB J 1998, 12(9):633-651.
125.Ben-Porath I, Yanuka O, Benvenisty N: The tmp gene, encoding a membrane protein, is a c-Myc target with a tumorigenic activity. Mol Cell Biol 1999, 19(5):3529-3539.
126.Nilsson JA, Cleveland JL: Myc pathways provoking cell suicide and cancer. Oncogene 2003, 22(56):9007-9021.
127.Adams JM, Cory S: Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci 2001, 26(1):61-66.
128.Strasser A, O''Connor L, Dixit VM: Apoptosis signaling. Annu Rev Biochem 2000, 69:217-245.
129.Antonsson B, Montessuit S, Sanchez B, Martinou JC: Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J Biol Chem 2001, 276(15):11615-11623.
130.Huang DC, Strasser A: BH3-Only proteins-essential initiators of apoptotic cell death. Cell 2000, 103(6):839-842.
131.Borner C: The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol 2003, 39(11):615-647.
132.Cory S, Huang DC, Adams JM: The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene 2003, 22(53):8590-8607.
133.Zou H, Henzel WJ, Liu X, Lutschg A, Wang X: Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 1997, 90(3):405-413.
134.Wilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA, Murcko MA, Chambers SP, Aldape RA, Raybuck SA et al: Structure and mechanism of interleukin-1 beta converting enzyme. Nature 1994, 370(6487):270-275.
135.Thornberry NA, Lazebnik Y: Caspases: enemies within. Science 1998, 281(5381):1312-1316.
136.Oliver FJ, de la Rubia G, Rolli V, Ruiz-Ruiz MC, de Murcia G, Murcia JM: Importance of poly(ADP-ribose) polymerase and its cleavage in apoptosis. Lesson from an uncleavable mutant. J Biol Chem 1998, 273(50):33533-33539.
137.Orth K, Chinnaiyan AM, Garg M, Froelich CJ, Dixit VM: The CED-3/ICE-like protease Mch2 is activated during apoptosis and cleaves the death substrate lamin A. J Biol Chem 1996, 271(28):16443-16446.
138.Wolf BB, Schuler M, Echeverri F, Green DR: Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated DNase inactivation. J Biol Chem 1999, 274(43):30651-30656.
139.Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S: A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 1998, 391(6662):43-50.
140.Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J et al: A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 1992, 356(6372):768-774.
141.Degterev A, Boyce M, Yuan J: A decade of caspases. Oncogene 2003, 22(53):8543-8567.
142.Johnson GL, Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002, 298(5600):1911-1912.
143.Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995, 270(5240):1326-1331.
144.Zhu Y, Mao XO, Sun Y, Xia Z, Greenberg DA: p38 Mitogen-activated protein kinase mediates hypoxic regulation of Mdm2 and p53 in neurons. J Biol Chem 2002, 277(25):22909-22914.
145.Orlov SN, Dam TV, Tremblay J, Hamet P: Apoptosis in vascular smooth muscle cells: role of cell shrinkage. Biochem Biophys Res Commun 1996, 221(3):708-715.
146.Walsh K, Isner JM: Apoptosis in inflammatory-fibroproliferative disorders of the vessel wall. Cardiovasc Res 2000, 45(3):756-765.
147.Nobuyoshi M, Kimura T, Ohishi H, Horiuchi H, Nosaka H, Hamasaki N, Yokoi H, Kim K: Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients. J Am Coll Cardiol 1991, 17(2):433-439.
148.Clowes AW, Schwartz SM: Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res 1985, 56(1):139-145.
149.Pollman MJ, Yamada T, Horiuchi M, Gibbons GH: Vasoactive substances regulate vascular smooth muscle cell apoptosis. Countervailing influences of nitric oxide and angiotensin II. Circ Res 1996, 79(4):748-756.
150.Sata M, Perlman H, Muruve DA, Silver M, Ikebe M, Libermann TA, Oettgen P, Walsh K: Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response. Proc Natl Acad Sci U S A 1998, 95(3):1213-1217.
151.Lisi DM: Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. N Engl J Med 1997, 337(26):1919.
152.Yokoi H, Daida H, Kuwabara Y, Nishikawa H, Takatsu F, Tomihara H, Nakata Y, Kutsumi Y, Ohshima S, Nishiyama S et al: Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial. J Am Coll Cardiol 1997, 30(4):855-862.
153.Pollman MJ, Hall JL, Gibbons GH: Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty injury. Influence of redox state and cell phenotype. Circ Res 1999, 84(1):113-121.
154.Bennett MR, Evan GI, Schwartz SM: Apoptosis of rat vascular smooth muscle cells is regulated by p53-dependent and -independent pathways. Circ Res 1995, 77(2):266-273.
155.Scudiero DA, Shoemaker RH, Paull KD, Monks A, Tierney S, Nofziger TH, Currens MJ, Seniff D, Boyd MR: Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 1988, 48(17):4827-4833.
156.Peng CH, Huang CN, Hsu SP, Wang CJ: Penta-acetyl geniposide induce apoptosis in C6 glioma cells by modulating the activation of neutral sphingomyelinase-induced p75 nerve growth factor receptor and protein kinase Cdelta pathway. Mol Pharmacol 2006, 70(3):997-1004.
157.Lin HH, Huang HP, Huang CC, Chen JH, Wang CJ: Hibiscus polyphenol-rich extract induces apoptosis in human gastric carcinoma cells via p53 phosphorylation and p38 MAPK/FasL cascade pathway. Mol Carcinog 2005, 43(2):86-99.
158.Jiang K, Sun J, Cheng J, Djeu JY, Wei S, Sebti S: Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. Mol Cell Biol 2004, 24(12):5565-5576.
159.Jacob T, Ascher E, Alapat D, Olevskaia Y, Hingorani A: Activation of p38MAPK signaling cascade in a VSMC injury model: role of p38MAPK inhibitors in limiting VSMC proliferation. Eur J Vasc Endovasc Surg 2005, 29(5):470-478.
160.Lee B, Moon SK: Ras/ERK signaling pathway mediates activation of the p21WAF1 gene promoter in vascular smooth muscle cells by platelet-derived growth factor. Arch Biochem Biophys 2005, 443(1-2):113-119.
161.Tanski WJ, Nicholl SM, Kim D, Fegley AJ, Roztocil E, Davies MG: Sphingosine-1-phosphate-induced smooth muscle cell migration involves the mammalian target of rapamycin. J Vasc Surg 2005, 41(1):91-98.
162.Nath P, Eynott P, Leung SY, Adcock IM, Bennett BL, Chung KF: Potential role of c-Jun NH2-terminal kinase in allergic airway inflammation and remodelling: effects of SP600125. Eur J Pharmacol 2005, 506(3):273-283.
163.Kashiwakura Y, Watanabe M, Kusumi N, Sumiyoshi K, Nasu Y, Yamada H, Sawamura T, Kumon H, Takei K, Daida H: Dynamin-2 regulates oxidized low-density lipoprotein-induced apoptosis of vascular smooth muscle cell. Circulation 2004, 110(21):3329-3334.
164.Wang HG, Rapp UR, Reed JC: Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell 1996, 87(4):629-638.
165.Jin S, Zhuo Y, Guo W, Field J: p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association. J Biol Chem 2005, 280(26):24698-24705.
166.Zhong J, Troppmair J, Rapp UR: Independent control of cell survival by Raf-1 and Bcl-2 at the mitochondria. Oncogene 2001, 20(35):4807-4816.
167.Sohn D, Graupner V, Neise D, Essmann F, Schulze-Osthoff K, Janicke RU: Pifithrin-alpha protects against DNA damage-induced apoptosis downstream of mitochondria independent of p53. Cell Death Differ 2009, 16(6):869-878.
168.Galluzzi L, Morselli E, Kepp O, Tajeddine N, Kroemer G: Targeting p53 to mitochondria for cancer therapy. Cell Cycle 2008, 7(13):1949-1955.
169.Marchenko ND, Zaika A, Moll UM: Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem 2000, 275(21):16202-16212.
170.Murphy ME, Leu JI, George DL: p53 moves to mitochondria: a turn on the path to apoptosis. Cell Cycle 2004, 3(7):836-839.
171.Leu JI, George DL: Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria. Genes Dev 2007, 21(23):3095-3109.
172.Jiang P, Du W, Heese K, Wu M: The Bad guy cooperates with good cop p53: Bad is transcriptionally up-regulated by p53 and forms a Bad/p53 complex at the mitochondria to induce apoptosis. Mol Cell Biol 2006, 26(23):9071-9082.
173.Park BS, Song YS, Yee SB, Lee BG, Seo SY, Park YC, Kim JM, Kim HM, Yoo YH: Phospho-ser 15-p53 translocates into mitochondria and interacts with Bcl-2 and Bcl-xL in eugenol-induced apoptosis. Apoptosis 2005, 10(1):193-200.
174.Chulu JL, Lee LH, Lee YC, Liao SH, Lin FL, Shih WL, Liu HJ: Apoptosis induction by avian reovirus through p53 and mitochondria-mediated pathway. Biochem Biophys Res Commun 2007, 356(3):529-535.
175.Schuler M, Maurer U, Goldstein JC, Breitenbucher F, Hoffarth S, Waterhouse NJ, Green DR: p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation. Cell Death Differ 2003, 10(4):451-460.
176.Deng Y, Wu X: Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria. Proc Natl Acad Sci U S A 2000, 97(22):12050-12055.
177.Lee SK, Kim YC, Song SB, Kim YS: Stabilization and translocation of p53 to mitochondria is linked to Bax translocation to mitochondria in simvastatin-induced apoptosis. Biochem Biophys Res Commun 2010, 391(4):1592-1597.
178.Yang H, Li TW, Ko KS, Xia M, Lu SC: Switch from Mnt-Max to Myc-Max induces p53 and cyclin D1 expression and apoptosis during cholestasis in mouse and human hepatocytes. Hepatology 2009, 49(3):860-870.
179.Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV: A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 1999, 285(5434):1733-1737.
180.Strom E, Sathe S, Komarov PG, Chernova OB, Pavlovska I, Shyshynova I, Bosykh DA, Burdelya LG, Macklis RM, Skaliter R et al: Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol 2006, 2(9):474-479.
181.Marchenko ND, Wolff S, Erster S, Becker K, Moll UM: Monoubiquitylation promotes mitochondrial p53 translocation. EMBO J 2007, 26(4):923-934.
182.Shah MA, Schwartz GK: Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. Clin Cancer Res 2001, 7(8):2168-2181.
183.Wang CJ, Hsieh YJ, Chu CY, Lin YL, Tseng TH: Inhibition of cell cycle progression in human leukemia HL-60 cells by esculetin. Cancer Lett 2002, 183(2):163-168.
184.Koepp DM, Harper JW, Elledge SJ: How the cyclin became a cyclin: regulated proteolysis in the cell cycle. Cell 1999, 97(4):431-434.
185.Hunter T, Pines J: Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell 1994, 79(4):573-582.
186.Hunter T, Pines J: Cyclins and cancer. Cell 1991, 66(6):1071-1074.
187.Halaban R: Melanoma cell autonomous growth: the Rb/E2F pathway. Cancer Metastasis Rev 1999, 18(3):333-343.
188.Laskey RA, Fairman MP, Blow JJ: S phase of the cell cycle. Science 1989, 246(4930):609-614.
189.Hao XF, Alphey L, Bandara LR, Lam EW, Glover D, La Thangue NB: Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster. J Cell Sci 1995, 108 ( Pt 9):2945-2954.
190.Tyson JJ, Novak B, Odell GM, Chen K, Thron CD: Chemical kinetic theory: understanding cell-cycle regulation. Trends Biochem Sci 1996, 21(3):89-96.
191.McGill CJ, Brooks G: Cell cycle control mechanisms and their role in cardiac growth. Cardiovasc Res 1995, 30(4):557-569.
192.Li JM, Brooks G: Cell cycle regulatory molecules (cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors) and the cardiovascular system; potential targets for therapy? Eur Heart J 1999, 20(6):406-420.
193.Martinez AM, Afshar M, Martin F, Cavadore JC, Labbe JC, Doree M: Dual phosphorylation of the T-loop in cdk7: its role in controlling cyclin H binding and CAK activity. EMBO J 1997, 16(2):343-354.
194.Andersen G, Busso D, Poterszman A, Hwang JR, Wurtz JM, Ripp R, Thierry JC, Egly JM, Moras D: The structure of cyclin H: common mode of kinase activation and specific features. EMBO J 1997, 16(5):958-967.
195.Wolgemuth DJ, Lele KM, Jobanputra V, Salazar G: The A-type cyclins and the meiotic cell cycle in mammalian male germ cells. Int J Androl 2004, 27(4):192-199.
196.el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell 1993, 75(4):817-825.
197.Funk JO, Galloway DA: Inhibiting CDK inhibitors: new lessons from DNA tumor viruses. Trends Biochem Sci 1998, 23(9):337-341.
198.Sherr CJ: Cancer cell cycles. Science 1996, 274(5293):1672-1677.
199.Nevins JR: E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 1992, 258(5081):424-429.
200.van der Sman J, Thomas NS, Lam EW: Modulation of E2F complexes during G0 to S phase transition in human primary B-lymphocytes. J Biol Chem 1999, 274(17):12009-12016.
201.Beijersbergen RL, Kerkhoven RM, Zhu L, Carlee L, Voorhoeve PM, Bernards R: E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes Dev 1994, 8(22):2680-2690.
202.Ginsberg D, Vairo G, Chittenden T, Xiao ZX, Xu G, Wydner KL, DeCaprio JA, Lawrence JB, Livingston DM: E2F-4, a new member of the E2F transcription factor family, interacts with p107. Genes Dev 1994, 8(22):2665-2679.
203.Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D: The subcellular localization of E2F-4 is cell-cycle dependent. Proc Natl Acad Sci U S A 1997, 94(10):5095-5100.
204.Chen J, Lin J, Levine AJ: Regulation of transcription functions of the p53 tumor suppressor by the mdm-2 oncogene. Mol Med 1995, 1(2):142-152.
205.Danovi D, Meulmeester E, Pasini D, Migliorini D, Capra M, Frenk R, de Graaf P, Francoz S, Gasparini P, Gobbi A et al: Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol 2004, 24(13):5835-5843.
206.Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS, 3rd, Johnson BE, Skolnick MH: A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994, 264(5157):436-440.
207.Shibata K, Tanaka S, Shiraishi T, Kitano S, Mori M: G-protein gamma 7 is down-regulated in cancers and associated with p 27kip1-induced growth arrest. Cancer Res 1999, 59(5):1096-1101.
208.Wang Z, Van Tuyle G, Conrad D, Fisher PB, Dent P, Grant S: Dysregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/MDA6 increases the susceptibility of human leukemia cells (U937) to 1-beta-D-arabinofuranosylcytosine-mediated mitochondrial dysfunction and apoptosis. Cancer Res 1999, 59(6):1259-1267.
209.Yeargin J, Cheng J, Yu AL, Gjerset R, Bogart M, Haas M: P53 mutation in acute T cell lymphoblastic leukemia is of somatic origin and is stable during establishment of T cell acute lymphoblastic leukemia cell lines. J Clin Invest 1993, 91(5):2111-2117.
210.Toyoshima H, Hunter T: p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 1994, 78(1):67-74.
211.Lorenzoni R, Gistri R, Cecchi F, Olivotto I, Chiriatti G, Elliott P, McKenna WJ, Camici PG: Syncope and ventricular arrhythmias in hypertrophic cardiomyopathy are not related to the derangement of coronary microvascular function. Eur Heart J 1997, 18(12):1946-1950.
212.Giaid A: Nitric oxide and endothelin-1 in pulmonary hypertension. Chest 1998, 114(3 Suppl):208S-212S.
213.Warren JB, Brady AJ, Taylor GW: Vascular smooth muscle influences the release of endothelium-derived relaxing factor. Proc Biol Sci 1990, 241(1301):127-131.
214.Raij L: Nitric oxide in hypertension: relationship with renal injury and left ventricular hypertrophy. Hypertension 1998, 31(1 Pt 2):189-193.
215.Fabricius M, Rubin I, Bundgaard M, Lauritzen M: NOS activity in brain and endothelium: relation to hypercapnic rise of cerebral blood flow in rats. Am J Physiol 1996, 271(5 Pt 2):H2035-2044.
216.Boulanger CM, Heymes C, Benessiano J, Geske RS, Levy BI, Vanhoutte PM: Neuronal nitric oxide synthase is expressed in rat vascular smooth muscle cells: activation by angiotensin II in hypertension. Circ Res 1998, 83(12):1271-1278.
217.殷麒超: 超氧陰離子對血管平滑肌之一氧化氮生物活性的影響. 國立中正大學化學工程所 2007.
218.Kibbe M, Billiar T, Tzeng E: Inducible nitric oxide synthase and vascular injury. Cardiovasc Res 1999, 43(3):650-657.
219.Hecker M, Cattaruzza M, Wagner AH: Regulation of inducible nitric oxide synthase gene expression in vascular smooth muscle cells. Gen Pharmacol 1999, 32(1):9-16.
220.Yang Z, Wang S: [Relationship between nitric oxide synthase, endothelin and the initiation of hypertension and atherosclerosis]. Hua Xi Yi Ke Da Xue Xue Bao 1998, 29(2):160-164.
221.Oemar BS, Tschudi MR, Godoy N, Brovkovich V, Malinski T, Luscher TF: Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation 1998, 97(25):2494-2498.
222.Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, Imaizumi T: Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999, 99(9):1141-1146.
223.Dulak J, Tomala K, Loboda A, Jozkowicz A: Nitric oxide-dependent synthesis of vascular endothelial growth factor is impaired by high glucose. Life Sci 2004, 75(21):2573-2586.
224.Hardie DG, Scott JW, Pan DA, Hudson ER: Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett 2003, 546(1):113-120.
225.Hawley SA, Davison M, Woods A, Davies SP, Beri RK, Carling D, Hardie DG: Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem 1996, 271(44):27879-27887.
226.Davies SP, Helps NR, Cohen PT, Hardie DG: 5''-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 1995, 377(3):421-425.
227.Rutter GA, Da Silva Xavier G, Leclerc I: Roles of 5''-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochem J 2003, 375(Pt 1):1-16.
228.Corton JM, Gillespie JG, Hawley SA, Hardie DG: 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 1995, 229(2):558-565.
229.Aschenbach WG, Sakamoto K, Goodyear LJ: 5'' adenosine monophosphate-activated protein kinase, metabolism and exercise. Sports Med 2004, 34(2):91-103.
230.Towler MC, Hardie DG: AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res 2007, 100(3):328-341.
231.Feng Z, Zhang H, Levine AJ, Jin S: The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A 2005, 102(23):8204-8209.
232.Hoyer-Hansen M, Jaattela M: AMP-activated protein kinase: a universal regulator of autophagy? Autophagy 2007, 3(4):381-383.
233.Brito PM, Devillard R, Negre-Salvayre A, Almeida LM, Dinis TC, Salvayre R, Auge N: Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells. Atherosclerosis 2009, 205(1):126-134.
234.Ratnovsky A, Mellema M, An SS, Fredberg JJ, Shore SA: Airway smooth muscle proliferation and mechanics: effects of AMP kinase agonists. Mol Cell Biomech 2007, 4(3):143-157.
235.Nagata D, Takeda R, Sata M, Satonaka H, Suzuki E, Nagano T, Hirata Y: AMP-activated protein kinase inhibits angiotensin II-stimulated vascular smooth muscle cell proliferation. Circulation 2004, 110(4):444-451.
236.Rubin LJ, Magliola L, Feng X, Jones AW, Hale CC: Metabolic activation of AMP kinase in vascular smooth muscle. J Appl Physiol 2005, 98(1):296-306.
237.Chen ZP, Mitchelhill KI, Michell BJ, Stapleton D, Rodriguez-Crespo I, Witters LA, Power DA, Ortiz de Montellano PR, Kemp BE: AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett 1999, 443(3):285-289.
238.Nagata D, Mogi M, Walsh K: AMP-activated protein kinase (AMPK) signaling in endothelial cells is essential for angiogenesis in response to hypoxic stress. J Biol Chem 2003, 278(33):31000-31006.
239.Almeida A, Cidad P, Delgado-Esteban M, Fernandez E, Garcia-Nogales P, Bolanos JP: Inhibition of mitochondrial respiration by nitric oxide: its role in glucose metabolism and neuroprotection. J Neurosci Res 2005, 79(1-2):166-171.
240.Dixit M, Bess E, Fisslthaler B, Hartel FV, Noll T, Busse R, Fleming I: Shear stress-induced activation of the AMP-activated protein kinase regulates FoxO1a and angiopoietin-2 in endothelial cells. Cardiovasc Res 2008, 77(1):160-168.
241.Fisslthaler B, Fleming I, Keseru B, Walsh K, Busse R: Fluid shear stress and NO decrease the activity of the hydroxy-methylglutaryl coenzyme A reductase in endothelial cells via the AMP-activated protein kinase and FoxO1. Circ Res 2007, 100(2):e12-21.
242.Nagata D, Hirata Y: The role of AMP-activated protein kinase in the cardiovascular system. Hypertens Res, 33(1):22-28.
243.Stuehr DJ, Nathan CF: Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 1989, 169(5):1543-1555.
244.Hardie DG: AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007, 8(10):774-785.
245.Wever RM, Luscher TF, Cosentino F, Rabelink TJ: Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 1998, 97(1):108-112.
246.Albina JE, Reichner JS: Role of nitric oxide in mediation of macrophage cytotoxicity and apoptosis. Cancer Metastasis Rev 1998, 17(1):39-53.
247.Chae IH, Park KW, Kim HS, Oh BH: Nitric oxide-induced apoptosis is mediated by Bax/Bcl-2 gene expression, transition of cytochrome c, and activation of caspase-3 in rat vascular smooth muscle cells. Clin Chim Acta 2004, 341(1-2):83-91.
248.Pilane CM, Labelle EF: Nitric oxide stimulated vascular smooth muscle cells undergo apoptosis induced in part by arachidonic acid derived eicosanoids. J Cell Physiol 2005, 204(2):423-427.
249.Doronzo G, Russo I, Mattiello L, Anfossi G, Bosia A, Trovati M: Insulin activates vascular endothelial growth factor in vascular smooth muscle cells: influence of nitric oxide and of insulin resistance. Eur J Clin Invest 2004, 34(10):664-673.
250.Haider A, Lee I, Grabarek J, Darzynkiewicz Z, Ferreri NR: Dual functionality of cyclooxygenase-2 as a regulator of tumor necrosis factor-mediated G1 shortening and nitric oxide-mediated inhibition of vascular smooth muscle cell proliferation. Circulation 2003, 108(8):1015-1021.
251.Kibbe MR, Li J, Nie S, Watkins SC, Lizonova A, Kovesdi I, Simmons RL, Billiar TR, Tzeng E: Inducible nitric oxide synthase (iNOS) expression upregulates p21 and inhibits vascular smooth muscle cell proliferation through p42/44 mitogen-activated protein kinase activation and independent of p53 and cyclic guanosine monophosphate. J Vasc Surg 2000, 31(6):1214-1228.
252.Chamley JH, Groschel-Stewart U, Campbell GR, Burnstock G: Distinction between smooth muscle, fibroblasts and endothelial cells in culture by the use of fluoresceinated antibodies against smooth muscle actin. Cell Tissue Res 1977, 177(4):445-457.
253.Chamley-Campbell JH, Campbell GR, Ross R: Phenotype-dependent response of cultured aortic smooth muscle to serum mitogens. J Cell Biol 1981, 89(2):379-383.
254.Schwartz SM, Campbell GR, Campbell JH: Replication of smooth muscle cells in vascular disease. Circ Res 1986, 58(4):427-444.
255.Luscher TF: Endothelium in the control of vascular tone and growth: role of local mediators and mechanical forces. Blood Press Suppl 1994, 1:18-22.
256.Raines EW: The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int J Exp Pathol 2000, 81(3):173-182.
257.Fager G, Camejo G, Olsson U, Ostergren-Lunden G, Bondjers G: Heparin-like glycosaminoglycans influence growth and phenotype of human arterial smooth muscle cells in vitro. II. The platelet-derived growth factor A-chain contains a sequence that specifically binds heparin. In Vitro Cell Dev Biol 1992, 28A(3 Pt 1):176-180.
258.Yamamoto M, Yamamoto K, Noumura T: Type I collagen promotes modulation of cultured rabbit arterial smooth muscle cells from a contractile to a synthetic phenotype. Exp Cell Res 1993, 204(1):121-129.
259.Khan R, Agrotis A, Bobik A: Understanding the role of transforming growth factor-beta1 in intimal thickening after vascular injury. Cardiovasc Res 2007, 74(2):223-234.
260.Fox GL, Rebay I, Hynes RO: Expression of DFak56, a Drosophila homolog of vertebrate focal adhesion kinase, supports a role in cell migration in vivo. Proc Natl Acad Sci U S A 1999, 96(26):14978-14983.
261.Schaller MD: Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta 2001, 1540(1):1-21.
262.Schaller MD, Parsons JT: Focal adhesion kinase and associated proteins. Curr Opin Cell Biol 1994, 6(5):705-710.
263.Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T: Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 1995, 377(6549):539-544.
264.Klemke RL, Leng J, Molander R, Brooks PC, Vuori K, Cheresh DA: CAS/Crk coupling serves as a "molecular switch" for induction of cell migration. J Cell Biol 1998, 140(4):961-972.
265.Campbell M, Trimble ER: Modification of PI3K- and MAPK-dependent chemotaxis in aortic vascular smooth muscle cells by protein kinase CbetaII. Circ Res 2005, 96(2):197-206.
266.Van Aelst L, D''Souza-Schorey C: Rho GTPases and signaling networks. Genes Dev 1997, 11(18):2295-2322.
267.Lim L, Manser E, Leung T, Hall C: Regulation of phosphorylation pathways by p21 GTPases. The p21 Ras-related Rho subfamily and its role in phosphorylation signalling pathways. Eur J Biochem 1996, 242(2):171-185.
268.Bourne HR, Sanders DA, McCormick F: The GTPase superfamily: a conserved switch for diverse cell functions. Nature 1990, 348(6297):125-132.
269.Bokoch GM, Der CJ: Emerging concepts in the Ras superfamily of GTP-binding proteins. FASEB J 1993, 7(9):750-759.
270.Hall A: Ras-related proteins. Curr Opin Cell Biol 1993, 5(2):265-268.
271.Downward J: The ras superfamily of small GTP-binding proteins. Trends Biochem Sci 1990, 15(12):469-472.
272.Bourne HR, Sanders DA, McCormick F: The GTPase superfamily: conserved structure and molecular mechanism. Nature 1991, 349(6305):117-127.
273.Sigal IS, Gibbs JB, D''Alonzo JS, Scolnick EM: Identification of effector residues and a neutralizing epitope of Ha-ras-encoded p21. Proc Natl Acad Sci U S A 1986, 83(13):4725-4729.
274.Adari H, Lowy DR, Willumsen BM, Der CJ, McCormick F: Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain. Science 1988, 240(4851):518-521.
275.Khwaja A: Akt is more than just a Bad kinase. Nature 1999, 401(6748):33-34.
276.Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, Sundaresan M, Finkel T, Goldschmidt-Clermont PJ: Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 1997, 275(5306):1649-1652.
277.Romashkova JA, Makarov SS: NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 1999, 401(6748):86-90.
278.Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 1999, 401(6748):82-85.
279.Mayo MW, Wang CY, Cogswell PC, Rogers-Graham KS, Lowe SW, Der CJ, Baldwin AS, Jr.: Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 1997, 278(5344):1812-1815.
280.Chien KR, Hoshijima M: Unravelling Ras signals in cardiovascular disease. Nat Cell Biol 2004, 6(9):807-808.
281.Burridge K, Wennerberg K: Rho and Rac take center stage. Cell 2004, 116(2):167-179.
282.Hall A: Rho GTPases and the actin cytoskeleton. Science 1998, 279(5350):509-514.
283.Kaverina I, Krylyshkina O, Small JV: Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol 2002, 34(7):746-761.
284.Amano M, Chihara K, Kimura K, Fukata Y, Nakamura N, Matsuura Y, Kaibuchi K: Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science 1997, 275(5304):1308-1311.
285.Seasholtz TM, Majumdar M, Kaplan DD, Brown JH: Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration. Circ Res 1999, 84(10):1186-1193.
286.Chen Z, Sun J, Pradines A, Favre G, Adnane J, Sebti SM: Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. J Biol Chem 2000, 275(24):17974-17978.
287.Du W, Prendergast GC: Geranylgeranylated RhoB mediates suppression of human tumor cell growth by farnesyltransferase inhibitors. Cancer Res 1999, 59(21):5492-5496.
288.Fritz G, Kaina B, Aktories K: The ras-related small GTP-binding protein RhoB is immediate-early inducible by DNA damaging treatments. J Biol Chem 1995, 270(42):25172-25177.
289.Jahner D, Hunter T: The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts. Mol Cell Biol 1991, 11(7):3682-3690.
290.Cox AD, Der CJ: Ras family signaling: therapeutic targeting. Cancer Biol Ther 2002, 1(6):599-606.
291.Barbacid M: ras genes. Annu Rev Biochem 1987, 56:779-827.
292.Jiang K, Delarue FL, Sebti SM: EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation. Oncogene 2004, 23(5):1136-1145.
293.Kapeller R, Prasad KV, Janssen O, Hou W, Schaffhausen BS, Rudd CE, Cantley LC: Identification of two SH3-binding motifs in the regulatory subunit of phosphatidylinositol 3-kinase. J Biol Chem 1994, 269(3):1927-1933.
294.Welham MJ, Dechert U, Leslie KB, Jirik F, Schrader JW: Interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor, but not IL-4, induce tyrosine phosphorylation, activation, and association of SHPTP2 with Grb2 and phosphatidylinositol 3''-kinase. J Biol Chem 1994, 269(38):23764-23768.
295.Leevers SJ, Vanhaesebroeck B, Waterfield MD: Signalling through phosphoinositide 3-kinases: the lipids take centre stage. Curr Opin Cell Biol 1999, 11(2):219-225.
296.Goncharova EA, Ammit AJ, Irani C, Carroll RG, Eszterhas AJ, Panettieri RA, Krymskaya VP: PI3K is required for proliferation and migration of human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2002, 283(2):L354-363.
297.Isenovic ER, Kedees MH, Tepavcevic S, Milosavljevic T, Koricanac G, Trpkovic A, Marche P: Role of PI3K/AKT, cPLA2 and ERK1/2 signaling pathways in insulin regulation of vascular smooth muscle cells proliferation. Cardiovasc Hematol Disord Drug Targets 2009, 9(3):172-180.
298.Yang GY, Yao JS, Huey M, Hashimoto T, Young WL: Participation of PI3K and ERK1/2 pathways are required for human brain vascular smooth muscle cell migration. Neurochem Int 2004, 44(6):441-446.
299.Zhong H, May MJ, Jimi E, Ghosh S: The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 2002, 9(3):625-636.
300.Ghosh G, van Duyne G, Ghosh S, Sigler PB: Structure of NF-kappa B p50 homodimer bound to a kappa B site. Nature 1995, 373(6512):303-310.
301.Montaner S, Perona R, Saniger L, Lacal JC: Activation of serum response factor by RhoA is mediated by the nuclear factor-kappaB and C/EBP transcription factors. J Biol Chem 1999, 274(13):8506-8515.
302.Baldwin AS: Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest 2001, 107(3):241-246.
303.Perona R, Montaner S, Saniger L, Sanchez-Perez I, Bravo R, Lacal JC: Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins. Genes Dev 1997, 11(4):463-475.
304.De Martin R, Hoeth M, Hofer-Warbinek R, Schmid JA: The transcription factor NF-kappa B and the regulation of vascular cell function. Arterioscler Thromb Vasc Biol 2000, 20(11):E83-88.
305.Nagase H, Woessner JF, Jr.: Matrix metalloproteinases. J Biol Chem 1999, 274(31):21491-21494.
306.Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP: Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 1997, 74(2):111-122.
307.Visse R, Nagase H: Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003, 92(8):827-839.
308.Palanki MS: Inhibitors of AP-1 and NF-kappa B mediated transcriptional activation: therapeutic potential in autoimmune diseases and structural diversity. Curr Med Chem 2002, 9(2):219-227.
309.Yoshida M, Korfhagen TR, Whitsett JA: Surfactant protein D regulates NF-kappa B and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. J Immunol 2001, 166(12):7514-7519.
310.Aljada A, Ghanim H, Mohanty P, Hofmeyer D, Tripathy D, Dandona P: Hydrocortisone suppresses intranuclear activator-protein-1 (AP-1) binding activity in mononuclear cells and plasma matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). J Clin Endocrinol Metab 2001, 86(12):5988-5991.
311.Qin H, Sun Y, Benveniste EN: The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J Biol Chem 1999, 274(41):29130-29137.
312.Huang S, Bucana CD, Van Arsdall M, Fidler IJ: Stat1 negatively regulates angiogenesis, tumorigenicity and metastasis of tumor cells. Oncogene 2002, 21(16):2504-2512.
313.Jean D, Bar-Eli M: Targeting the ATF-1/CREB transcription factors by single chain Fv fragment in human melanoma: potential modality for cancer therapy. Crit Rev Immunol 2001, 21(1-3):275-286.
314.Pan MR, Hung WC: Nonsteroidal anti-inflammatory drugs inhibit matrix metalloproteinase-2 via suppression of the ERK/Sp1-mediated transcription. J Biol Chem 2002, 277(36):32775-32780.
315.Welch DR, Sakamaki T, Pioquinto R, Leonard TO, Goldberg SF, Hon Q, Erikson RL, Rieber M, Rieber MS, Hicks DJ et al: Transfection of constitutively active mitogen-activated protein/extracellular signal-regulated kinase kinase confers tumorigenic and metastatic potentials to NIH3T3 cells. Cancer Res 2000, 60(6):1552-1556.
316.Kubiatowski T, Jang T, Lachyankar MB, Salmonsen R, Nabi RR, Quesenberry PJ, Litofsky NS, Ross AH, Recht LD: Association of increased phosphatidylinositol 3-kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas. J Neurosurg 2001, 95(3):480-488.
317.Nagase H: Cell surface activation of progelatinase A (proMMP-2) and cell migration. Cell Res 1998, 8(3):179-186.
318.Zhang FL, Casey PJ: Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996, 65:241-269.
319.Casey PJ, Thissen JA, Moomaw JF: Enzymatic modification of proteins with a geranylgeranyl isoprenoid. Proc Natl Acad Sci U S A 1991, 88(19):8631-8635.
320.Seabra MC, Goldstein JL, Sudhof TC, Brown MS: Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys. J Biol Chem 1992, 267(20):14497-14503.
321.Yau L, Litchie B, Thomas S, Storie B, Yurkova N, Zahradka P: Endogenous mono-ADP-ribosylation mediates smooth muscle cell proliferation and migration via protein kinase N-dependent induction of c-fos expression. Eur J Biochem 2003, 270(1):101-110.
322.Cheng XW, Kuzuya M, Nakamura K, Liu Z, Di Q, Hasegawa J, Iwata M, Murohara T, Yokota M, Iguchi A: Mechanisms of the inhibitory effect of epigallocatechin-3-gallate on cultured human vascular smooth muscle cell invasion. Arterioscler Thromb Vasc Biol 2005, 25(9):1864-1870.
323.Chen PN, Hsieh YS, Chiou HL, Chu SC: Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways. Chem Biol Interact 2005, 156(2-3):141-150.
324.Menendez JA, Mehmi I, Atlas E, Colomer R, Lupu R: Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: Role of exogenous dietary fatty acids, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB. Int J Oncol 2004, 24(3):591-608.
325.Hommelberg PP, Plat J, Langen RC, Schols AM, Mensink RP: Fatty acid-induced NF-kappaB activation and insulin resistance in skeletal muscle are chain length dependent. Am J Physiol Endocrinol Metab 2009, 296(1):E114-120.
326.陳書郡: 桑葉多酚萃取物減少肝臟脂肪堆積之作用. 中山醫學大學生化暨生物科技研究所碩士論文 2009.
327.Haklai R, Weisz MG, Elad G, Paz A, Marciano D, Egozi Y, Ben-Baruch G, Kloog Y: Dislodgment and accelerated degradation of Ras. Biochemistry 1998, 37(5):1306-1314.
328.Indolfi C, Avvedimento EV, Rapacciuolo A, Di Lorenzo E, Esposito G, Stabile E, Feliciello A, Mele E, Giuliano P, Condorelli G et al: Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo. Nat Med 1995, 1(6):541-545.
329.Wang H, Liu B, Fu M, Zeng C: [Transcriptional expression of oncogenes and Rb antioncogene in experimental atherosclerotic lesions]. Hua Xi Yi Ke Da Xue Xue Bao 1996, 27(2):117-121.
330.Yang CM, Chiu CT, Wang CC, Chien CS, Hsiao LD, Lin CC, Tu MT, Pan SL: Activation of mitogen-activated protein kinase by oxidized low-density lipoprotein in canine cultured vascular smooth muscle cells. Cell Signal 2000, 12(4):205-214.
331.Chen KH, Guo X, Ma D, Guo Y, Li Q, Yang D, Li P, Qiu X, Wen S, Xiao RP et al: Dysregulation of HSG triggers vascular proliferative disorders. Nat Cell Biol 2004, 6(9):872-883.
332.Hayflick L, Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res 1961, 25:585-621.
333.Hayflick L: The Limited in Vitro Lifetime of Human Diploid Cell Strains. Exp Cell Res 1965, 37:614-636.
334.Hadshiew IM, Eller MS, Gilchrest BA: Skin aging and photoaging: the role of DNA damage and repair. Am J Contact Dermat 2000, 11(1):19-25.
335.Oshimura M, Barrett JC: Multiple pathways to cellular senescence: role of telomerase repressors. Eur J Cancer 1997, 33(5):710-715.
336.Carman TA, Afshari CA, Barrett JC: Cellular senescence in telomerase-expressing Syrian hamster embryo cells. Exp Cell Res 1998, 244(1):33-42.
337.Kipling D: Telomeres, replicative senescence and human ageing. Maturitas 2001, 38(1):25-37; discussion 37-28.
338.Campisi J: The biology of replicative senescence. Eur J Cancer 1997, 33(5):703-709.
339.Weilbaecher RG, Lundblad V: Assembly and regulation of telomerase. Curr Opin Chem Biol 1999, 3(5):573-577.
340.Stein GH, Dulic V: Molecular mechanisms for the senescent cell cycle arrest. J Investig Dermatol Symp Proc 1998, 3(1):14-18.
341.Granger MP, Wright WE, Shay JW: Telomerase in cancer and aging. Crit Rev Oncol Hematol 2002, 41(1):29-40.
342.Henderson S, Allsopp R, Spector D, Wang SS, Harley C: In situ analysis of changes in telomere size during replicative aging and cell transformation. J Cell Biol 1996, 134(1):1-12.
343.Patterson H: Approaches to proto-oncogene and tumour suppressor gene identification. Eur J Cancer 1992, 28(1):258-263.
344.Foreman KE, Tang J: Molecular mechanisms of replicative senescence in endothelial cells. Exp Gerontol 2003, 38(11-12):1251-1257.
345.Blander G, de Oliveira RM, Conboy CM, Haigis M, Guarente L: Superoxide dismutase 1 knock-down induces senescence in human fibroblasts. J Biol Chem 2003, 278(40):38966-38969.
346.Brown JP, Wei W, Sedivy JM: Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 1997, 277(5327):831-834.
347.Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O et al: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 1995, 92(20):9363-9367.
348.Krishna DR, Sperker B, Fritz P, Klotz U: Does pH 6 beta-galactosidase activity indicate cell senescence? Mech Ageing Dev 1999, 109(2):113-123.
349.Gorenne I, Kavurma M, Scott S, Bennett M: Vascular smooth muscle cell senescence in atherosclerosis. Cardiovasc Res 2006, 72(1):9-17.
350.Bonin LR, Madden K, Shera K, Ihle J, Matthews C, Aziz S, Perez-Reyes N, McDougall JK, Conroy SC: Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque. Arterioscler Thromb Vasc Biol 1999, 19(3):575-587.
351.Minamino T, Yoshida T, Tateno K, Miyauchi H, Zou Y, Toko H, Komuro I: Ras induces vascular smooth muscle cell senescence and inflammation in human atherosclerosis. Circulation 2003, 108(18):2264-2269.
352.Matthews C, Gorenne I, Scott S, Figg N, Kirkpatrick P, Ritchie A, Goddard M, Bennett M: Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ Res 2006, 99(2):156-164.
353.Min LJ, Mogi M, Tamura K, Iwanami J, Sakata A, Fujita T, Tsukuda K, Jing F, Iwai M, Horiuchi M: Angiotensin II type 1 receptor-associated protein prevents vascular smooth muscle cell senescence via inactivation of calcineurin/nuclear factor of activated T cells pathway. J Mol Cell Cardiol 2009, 47(6):798-809.
354.Mahmoudi M, Gorenne I, Mercer J, Figg N, Littlewood T, Bennett M: Statins use a novel Nijmegen breakage syndrome-1-dependent pathway to accelerate DNA repair in vascular smooth muscle cells. Circ Res 2008, 103(7):717-725.
355.Ragnauth CD, Warren DT, Liu Y, McNair R, Tajsic T, Figg N, Shroff R, Skepper J, Shanahan CM: Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 2010, 121(20):2200-2210.




QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔