臺灣博碩士論文加值系統

脂質代謝是維持正常生理功能及生命所必須。然而在已開發或開發中國家，脂質代謝的失調，或稱脂質代謝異常卻逐漸成為一個嚴重的健康問題。高血脂症：諸如高三酸甘油脂或是高膽固醇是最常見的一種脂質代謝異常並且常伴隨著肥胖或是粥狀動脈硬化的發生。近年來，臨床上對於這類疾病的用藥治療已經轉移到改善與其相關的脂質代謝異常上。而在最近幾年，中藥在預防人類疾病的使用上也逐漸受到關注。漢黃芩素是中藥黃芩的主要萃取物之一，並且已經被報導具有許多不同的抗發炎及抗氧化的功效。然而，漢黃芩素對於脂肪細胞中三酸甘油脂的代謝及巨噬細胞中膽固醇的代謝的影響至今仍未十分明瞭。因此在本篇研究中，我們主要是針對漢黃芩素對於這兩個脂質代謝途徑的探討及其可能參與的機制。我們發現漢黃芩素並不會改變3T3-L1前脂肪細胞的生長及分化。然而，在成熟的脂肪細胞中，漢黃芩素會透過蛋白質激?，來刺激脂質分解的速率。而在正常老鼠中，漢黃芩素同樣會影響脂質的代謝，包括減少白色脂肪組織、增加高密度脂蛋白的膽固醇含量、降低血清中的三酸甘油脂、改變血中脂肪激素的含量、抑制脂肪生成相關蛋白的表現和促進脂質分解作用。由此結果可以得知，漢黃芩素在活體中不但具有調節脂質生成和脂質分解作用，並具有預防高血脂症的效果。在粥狀動脈硬化病變的形成中，巨噬細胞內會大量堆積膽固醇並形成泡沫細胞且調控膽固醇的代謝。而我們發現在巨噬細胞中，漢黃芩素的給予可以抑制氧化態低密度脂蛋白所造成的脂質堆積，且主要是透過了增加三磷酸腺?ㄤ畢X盒轉運體A1所驅使的膽固醇流出而達到此保護作用。我們也證實，蛋白質激?，和外源鈣/鈣調素依賴型激?〞滌T息傳遞路徑在漢黃芩素抑制泡沫細胞的形成和增加三磷酸腺?ㄤ畢X盒轉運體A1的表現等作用上扮演關鍵的角色。此外，漢黃芩素增加三磷酸腺?ㄤ畢X盒轉運體A1的蛋白表現量主要是增加了其蛋白質的穩定性，而非影響到其基因的轉錄。藉由使用免疫共沉澱的實驗方法及蛋白質去磷酸??B的抑制劑，我們也發現漢黃芩素延長三磷酸腺?ㄤ畢X盒轉運體A1的半衰期是經由增加其與蛋白質磷酸??B的結合而導致被去磷酸化所達到的，此結果也進而減緩了細胞內脂質的堆積。由此結果我們可以得知，漢黃芩素可以透過三磷酸腺?ㄤ畢X盒轉運體A1將膽固醇送出，而抑制泡沫細胞的形成。總的來說，本篇研究證實了漢黃芩素具有預防肥胖及治療粥狀動脈硬化的潛力。

Lipid metabolism is essential for maintenance of physiological function and life. However, dysregulation of lipid metabolism, also called lipid abnormality, has been considered as a severe health problem in developing or developed countries. Hyperlipidemia, including higher level of serum triglyceride or cholesterol, is the most common lipid abnormality and associates with the obesity and atherosclerosis. Over the past decade, the ultimate goal of clinical trails for therapy of obesity or atherosclerosis has been shifted to explore the new classes of agents, which also can provide protection against lipid abnormality. Recently, Chinese herbs have received increasing attention and been extensively used for the prevention of human diseases. Wogonin, the Scutellaria baicalensis Georgi extracts, have been reported to exert protective effects on inflammation and oxidative stress. However, effects of wogonin on triglyceride metabolism in adipocytes and cholesterol metabolism in macrophages are not fully understood. In the present study, we would like to investigate the effect of wogonin on these two processes. We examined that treatment of wogonin does not affect the proliferation and differentiation in 3T3-L1 preadipocytes. Additionally, wogonin administration significantly increased the adipocyte lipolysis through the protein kinase A (PKA)-dependent mechanism. The effects of wogonin on lipid metabolism, including decreased white adipose tissue mass, elevated high-density lipoprotein-cholesterol (HDL-c), reduced serum triglyceride, altered adipokine secretion and adipogenesis-related protein and enhanced lipolysis, were also defined in WT mice. These results suggest that wogonin modulates adipogenesis and lipolysis and preserves the preventive effects on hyperlipidemia. During atherogenesis, foam cells, which are characterized by the over-loaded cellular cholesterol in macrophages, play the critical role in cholesterol metabolism. Here, we showed that wogonin attenuated oxidized low-density lipoprotein (oxLDL)-induced cholesterol accumulation in macrophages. The suppressive effect of wogonin was due to the increase of ABCA1-dependent cholesterol efflux. Besides, activation of PKA and calcium/calmodulin-dependent protein kinase is necessary for the inhibitory effect of wogonin on formation of foam cell. Moreover, the up-regulation of ABCA1 protein by wogonin resulted from a decrease in degradation rate of ABCA1 protein, whereas wogonin did not affect the mRNA expression of ABCA1. We show that wogonin extended ABCA1 half-life via protein phosphatase 2B (PP2B)-mediated dephosphorylation, as evidenced by an increase in interaction between ABCA1 and PP2B. Otherwise, pharmacological inhibition of PP2B prevented wogonin-induced ABCA1 protein expression, dephosphorylation and attenuation of lipid accumulation. These results indicate that wogonin sufficiently inhibits the formation of macrophage foam cells via ABCA1-dependent cholesterol transport. Collectively, our study provides the potency of wogonin in the regulation of peripheral triglyceride and cholesterol metabolism.

中文摘要 I
英文摘要 III
目錄 VI
第一章 背景簡介 1
1.1 脂質代謝 2
1.1.1 肥胖 2
1.1.2 脂肪細胞 3
1.1.3 脂肪生成作用 4
1.1.4脂質分解 10
1.1.5三酸甘油脂與膽固醇代謝 17
1.2 膽固醇代謝 18
1.2.1粥狀動脈硬化 20
1.2.2泡沫細胞的形成 22
1.3黃芩 34
1.3.1黃芩素 35
1.3.2黃芩? 36
1.3.3漢黃芩素 37
1.4研究根據及目的 41
第二章 材料與方法 45
2.1材料與方法 46
2.1.1藥品與實驗測定套組 46
2.1.2細胞培養 47
2.1.3 MTT測定 48
2.1.4油紅O染色 48
2.1.5西方墨點法 49
2.1.6甘油的測定 50
2.1.7動物實驗 51
2.1.8血清生化數值測定 51
2.1.9脂肪素的測定 52
2.1.10組織學檢測 53
2.1.11低密度脂蛋白的氧化 54
2.1.12反轉錄聚合?○s鎖反應 54
2.1.13細胞內膽固醇及三酸甘油脂測定 55
2.1.14 Dil標定的氧化態低密度脂蛋白結合試驗 56
2.1.15膽固醇輸出實驗 56
2.1.16免疫沉澱 57
2.1.17統計分析 57
第三章 結果 59
3.1 探討黃芩萃取物：黃芩素、黃芩?ㄘM漢黃芩素在脂肪細胞和小鼠中對於三酸甘油脂的影響 60
3.1.1 黃芩萃取物：黃芩素、黃芩?ㄘM漢黃芩素不會影響到前脂肪細胞3T3-L1細胞株的生長 60
3.1.2黃芩素可以減少在分化液誘導的情況下脂肪細胞內脂質堆積的情形，而黃芩?ㄘM漢黃芩素則無此功效 60
3.1.3 前脂肪細胞在分化液的刺激下，只有黃芩素可以有效的減少與分化相關的轉錄因子和脂肪細胞所特有的蛋白質的表現 61
3.1.4漢黃芩素可以增加成熟脂肪細胞內脂質分解的速率 62
3.1.5漢黃芩素對於小鼠的體重、肥胖指數 (adiposity index)、血脂和脂肪素分泌的影響 64
3.1.6漢黃芩素可以降低脂質合成有關的蛋白的表現和促進體內脂質分解作用的進行，而不影響到脂肪細胞的增生，並有效的減少白色脂肪組織內脂肪細胞的大小 65
3.2探討黃芩萃取物：黃芩素、黃芩?ㄘM漢黃芩素對於由氧化態低密度脂蛋白所導致的泡沫細胞的形成及對膽固醇代謝的影響 67
3.2.1在氧化態低密度脂蛋白的刺激下，漢黃芩素可以有效的減少巨噬細胞內膽固醇堆積的情形和泡沫細胞的形成 67
3.2.2漢黃芩素的處理可以增加三磷酸腺?ㄤ畢X盒轉運體A1的表現並促進巨噬細胞內膽固醇的輸出 68
3.2.3漢黃芩素透過活化蛋白質激?，和第二型外源鈣/鈣調素依賴型激?〞滌T息傳遞來增加三磷酸腺?ㄤ畢X盒轉運體A1的表現 70
3.2.4漢黃芩素透過蛋白質去磷酸??B的訊息傳遞路徑而增加了三磷酸腺?ㄤ畢X盒轉運體A1的蛋白質穩定性 70
3.2.4去磷酸??B的訊息傳遞路徑在漢黃芩素抑制泡沫細胞的效果上扮演重要的角色 72
第四章 結果與討論 74
4.1 討論 75
4.2 結論 85
圖表 87
參考文獻 119

1. Martin S, Parton RG. Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol. 2006;7(5):373-378.
2. Friedman JM. A war on obesity, not the obese. Science. 2003;299(5608):856-858.
3. Jensen MD. Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S57-63.
4. Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-643.
5. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362(6423):801-809.
6. Shi Y, Burn P. Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat Rev Drug Discov. 2004;3(8):695-710.
7. Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation. 2004;109(23 Suppl 1):III39-43.
8. Froy O. Metabolism and circadian rhythms--implications for obesity. Endocr Rev. 2010;31(1):1-24.
9. Despr?臃 JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rod?臃-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008;28(6):1039-1049.
10. Marques BG, Hausman DB, Martin RJ. Association of fat cell size and paracrine growth factors in development of hyperplastic obesity. Am J Physiol. 1998;275(6 Pt 2):R1898-1908.
11. Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006;444(7121):847-853.
12. Lyon CJ, Law RE, Hsueh WA. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology. 2003;144(6):2195-2200.
13. Dyck DJ, Heigenhauser GJ, Bruce CR. The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity. Acta Physiol. 2006 ;186(1):5-16.
14. Sethi JK, Vidal-Puig AJ. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007;48(6):1253-1262.
15. Karalis KP, Giannogonas P, Kodela E, Koutmani Y, Zoumakis M, Teli T. Mechanisms of obesity and related pathology: linking immune responses to metabolic stress. FEBS J. 2009;276(20):5747-5754.
16. Spiegelman BM, Flier JS. Spiegelman BM, Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell. 1996 ;87(3):377-389.
17. Mandrup S, Lane MD. Regulating adipogenesis. J Biol Chem. 1997;272(9):5367-5370.
18. Yeh WC, McKnight SL. Regulation of adipose maturation and energy homeostasis. Curr Opin Cell Biol. 1995;7(6):885-890.
19. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 2006;7(12):885-896.
20. Scott RE, Florine DL, Wille JJ Jr, Yun K. Coupling of growth arrest and differentiation at a distinct state in the G1 phase of the cell cycle: GD. Proc Natl Acad Sci U S A. 1982;79(3):845-849.
21. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109(9):1125-1131.
22. Wang X, Sato R, Brown MS, Hua X, Goldstein JL. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 1994;77(1):53-62.
23. Kim JB, Wright HM, Wright M, Spiegelman BM. ADD1/SREBP1 activates PPAR? through the production of endogenous ligand. Proc Natl Acad Sci U S A. 1998;95(8):4333-4337.
24. Kim JB, Spiegelman BM. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 1996;10(9):1096-1107.
25. Fajas L, Schoonjans K, Gelman L, Kim JB, Najib J, Martin G, Fruchart JC, Briggs M, Spiegelman BM, Auwerx J. Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism. Mol Cell Biol. 1999;19(8):5495-5503.
26. Yeh WC, Cao Z, Classon M, McKnight SL. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 1995;9(2):168-181.
27. Tanaka T, Yoshida N, Kishimoto T, Akira S. Defective adipocyte differentiation in mice lacking the C/EBP? and/or C/EBP? gene. EMBO J. 1997;16(24):7432-7443.
28. Christy RJ, Kaestner KH, Geiman DE, Lane MD. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A. 1991;88(6):2593-2597.
29. Lin FT, Lane MD. Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes. Genes Dev. 1992;6(4):533-544.
30. Wang ND, Finegold MJ, Bradley A, Ou CN, Abdelsayed SV, Wilde MD, Taylor LR, Wilson DR, Darlington GJ. Impaired energy homeostasis in C/EBP? knockout mice. Science. 1995;269(5227):1108-1112.
31. Aranda A, Pascual A. Nuclear hormone receptors and gene expression. Physiol Rev. 2001;81(3):1269-1304.
32. Saladin R, Fajas L, Dana S, Halvorsen YD, Auwerx J, Briggs M. Differential regulation of peroxisome proliferator activated receptor gamma1 (PPAR??) and PPAR?? messenger RNA expression in the early stages of adipogenesis. Cell Growth Differ. 1999;10(1):43-48.
33. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. PPAR? is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell. 1999;4(4):611-617.
34. Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. Cross-regulation of C/EBP? and PPAR? controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell. 1999;3(2):151-158.
35. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR??, a lipid-activated transcription factor Cell. 1994;79(7):1147-1156.
36. Chmurzyńska A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet. 2006;47(1):39-48.
37. Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. mPPAR??: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994;8(10):1224-1234.
38. Christy RJ, Yang VW, Ntambi JM, Geiman DE, Landschulz WH, Friedman AD, Nakabeppu Y, Kelly TJ, Lane MD. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev. 1989 3(9):1323-1335.
39. Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, Wahli W, Noy N. Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol. 2002;22(14):5114-5127.
40. Shen WJ, Sridhar K, Bernlohr DA, Kraemer FB. Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein. Proc Natl Acad Sci U S A. 1999;96(10):5528-5532.
41. Shen WJ, Liang Y, Hong R, Patel S, Natu V, Sridhar K, Jenkins A, Bernlohr DA, Kraemer FB. Characterization of the functional interaction of adipocyte lipid-binding protein with hormone-sensitive lipase. J Biol Chem. 2001;276(52):49443-49448.
42. Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M, Uysal KT, Cao Q, Atsumi G, Malone H, Krishnan B, Minokoshi Y, Kahn BB, Parker RA, Hotamisligil GS. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab. 2005;1(2):107-119.
43. Furuhashi M, Tuncman G, G?宁g?刡 CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007;447(7147):959-965.
44. Layne MD, Patel A, Chen YH, Rebel VI, Carvajal IM, Pellacani A, Ith B, Zhao D, Schreiber BM, Yet SF, Lee ME, Storch J, Perrella MA. Role of macrophage-expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice. FASEB J. 2001;15(14):2733-2735.
45. Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS, Linton MF. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med. 2001;7(6):699-705.
46. Girard J, Perdereau D, Foufelle F, Prip-Buus C, Ferr? P. Regulation of lipogenic enzyme gene expression by nutrients and hormones. FASEB J. 1994;8(1):36-42.
47. Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, Kuhajda FP. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science. 2000;288(5475):2379-2381.
48. Kovacs P, Harper I, Hanson RL, Infante AM, Bogardus C, Tataranni PA, Baier LJ. A novel missense substitution (Val1483Ile) in the fatty acid synthase gene (FAS) is associated with percentage of body fat and substrate oxidation rates in nondiabetic Pima Indians. Diabetes. 2004;53(7):1915-1919.
49. Zechner R, Kienesberger PC, Haemmerle G, Zimmermann R, Lass A. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res. 2009;50(1):3-21.
50. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS. Regulation of lipolysis in adipocytes. Annu Rev Nutr. 2007;27:79-101.
51. Castan I, Wijkander J, Manganiello V, Degerman E. Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in rat adipocytes. Biochem J. 1999;339:281-289.
52. Long YC, Zierath JR. AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest. 2006;116(7):1776-1783.
53. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science. 2006;312(5774):734-737.
54. Schweiger M, Lass A, Zimmermann R, Eichmann TO, Zechner R. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. Am J Physiol Endocrinol Metab. 2009;297(2):E289-296.
55. Ahmadian M, Duncan RE, Varady KA, Frasson D, Hellerstein MK, Birkenfeld AL, Samuel VT, Shulman GI, Wang Y, Kang C, Sul HS. Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity. Diabetes. 2009;58(4):855-866.
56. Jaworski K, Ahmadian M, Duncan RE, Sarkadi-Nagy E, Varady KA, Hellerstein MK, Lee HY, Samuel VT, Shulman GI, Kim KH, de Val S, Kang C, Sul HS. AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency. Nat Med. 2009;15(2):159-168.
57. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A, Zechner R. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 2004;306(5700):1383-1386.
58. Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem. 2004;279(47):48968-48975.
59. Villena JA, Roy S, Sarkadi-Nagy E, Kim KH, Sul HS. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem. 2004;279(45):47066-47075.
60. Birner-Gruenberger R, Susani-Etzerodt H, Waldhuber M, Riesenhuber G, Schmidinger H, Rechberger G, Kollroser M, Strauss JG, Lass A, Zimmermann R, Haemmerle G, Zechner R, Hermetter A. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J Biol Chem. 2006;281(52):40236-40241.
61. Bartz R, Zehmer JK, Zhu M, Chen Y, Serrero G, Zhao Y, Liu P. Dynamic activity of lipid droplets: protein phosphorylation and GTP-mediated protein translocation. J Proteome Res. 2007;6(8):3256-3265.
62. Fredrikson G, Tornqvist H, Belfrage P. Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. Biochim Biophys Acta. 1986;876(2):288-293.
63. Holm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans. 2003;31:1120-1124.
64. Osterlund T, Danielsson B, Degerman E, Contreras JA, Edgren G, Davis RC, Schotz MC, Holm C. Domain-structure analysis of recombinant rat hormone-sensitive lipase. Biochem J. 1996;319:411-420.
65. Shen WJ, Patel S, Hong R, Kraemer FB. Hormone-sensitive lipase functions as an oligomer. Biochemistry. 20007;39(9):2392-2398.
66. Str?熞fors P, Bj?宁gell P, Belfrage P. Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin. Proc Natl Acad Sci U S A. 1984;81(11):3317-3321.
67. Str?熞fors P, Belfrage P. Phosphorylation of hormone-sensitive lipase by cyclic AMP-dependent protein kinase. J Biol Chem. 1983;258(24):15146-15152.
68. Greenberg AS, Shen WJ, Muliro K, Patel S, Souza SC, Roth RA, Kraemer FB. Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway. J Biol Chem. 2001;276(48):45456-45461.
69. Zmuda-Trzebiatowska E, Oknianska A, Manganiello V, Degerman E. Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes. Cell Signal. 2006;18(3):382-390.
70. Garton AJ, Campbell DG, Carling D, Hardie DG, Colbran RJ, Yeaman SJ. Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein kinase. A possible antilipolytic mechanism. Eur J Biochem. 1989;179(1):249-254.
71. Garton AJ, Yeaman SJ. Identification and role of the basal phosphorylation site on hormone-sensitive lipase. Eur J Biochem. 1990;191(1):245-250.
72. Kim JY, Tillison K, Lee JH, Rearick DA, Smas CM. The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for transactivation by PPARgamma. Am J Physiol Endocrinol Metab. 2006;291(1):E115-127.
73. Osuga J, Ishibashi S, Oka T, Yagyu H, Tozawa R, Fujimoto A, Shionoiri F, Yahagi N, Kraemer FB, Tsutsumi O, Yamada N. Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci U S A. 2000;97(2):787-792.
74. Harada K, Shen WJ, Patel S, Natu V, Wang J, Osuga J, Ishibashi S, Kraemer FB. Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice. Am J Physiol Endocrinol Metab. 2003;285(6):E1182-1195.
75. Okazaki H, Osuga J, Tamura Y, Yahagi N, Tomita S, Shionoiri F, Iizuka Y, Ohashi K, Harada K, Kimura S, Gotoda T, Shimano H, Yamada N, Ishibashi S. Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases. Diabetes. 2002;51(12):3368-3375.
76. Shen WJ, Yu Z, Patel S, Jue D, Liu LF, Kraemer FB Hormone-sensitive lipase modulates adipose metabolism through PPAR?? Biochim Biophys Acta. 2011;1811(1):9-16.
77. Lucas S, Tavernier G, Tiraby C, Mairal A, Langin D. Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis. J Lipid Res. 2003;44(1):154-163.
78. Lee MS, Kim CT, Kim Y. Green tea (-)-epigallocatechin-3-gallate reduces body weight with regulation of multiple genes expression in adipose tissue of diet-induced obese mice. Ann Nutr Metab. 2009;54(2):151-157.
79. An S, Han JI, Kim MJ, Park JS, Han JM, Baek NI, Chung HG, Choi MS, Lee KT, Jeong TS. Ethanolic extracts of Brassica campestris spp. rapa roots prevent high-fat diet-induced obesity via ??3)-adrenergic regulation of white adipocyte lipolytic activity. J Med Food. 2010;13(2):406-414.
80. Kraemer FB, Shen WJ. Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. J Lipid Res. 2002;43(10):1585-1594.
81. Fernandez C, Lindholm M, Krogh M, Lucas S, Larsson S, Osmark P, Berger K, Bor?聲 J, Fielding B, Frayn K, Holm C. Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice. Am J Physiol Endocrinol Metab. 2008;295(4): 820-831.
82. Londos C, Brasaemle DL, Schultz CJ, Segrest JP, Kimmel AR. Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin Cell Dev Biol. 1999;10(1):51-58.
83. Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets. J Biol Chem. 1991;266(17):11341-11346.
84. Brasaemle DL, Rubin B, Harten IA, Gruia-Gray J, Kimmel AR, Londos C. Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J Biol Chem. 2000;275(49):38486-38493.
85. Tansey JT, Huml AM, Vogt R, Davis KE, Jones JM, Fraser KA, Brasaemle DL, Kimmel AR, Londos C. Functional studies on native and mutated forms of perilipins. A role in protein kinase A-mediated lipolysis of triacylglycerols. J Biol Chem. 2003;278(10):8401-8406.
86. Tansey JT, Sztalryd C, Gruia-Gray J, Roush DL, Zee JV, Gavrilova O, Reitman ML, Deng CX, Li C, Kimmel AR, Londos C. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci U S A. 2001;98(11):6494-6499.
87. Martinez-Botas J, Anderson JB, Tessier D, Lapillonne A, Chang BH, Quast MJ, Gorenstein D, Chen KH, Chan L. Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice. Nat Genet. 2000;26(4):474-479.
88. Kennelly PJ, Krebs EG. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991;266(24):15555-15558.
89. Bossemeyer D. Protein kinases--structure and function. FEBS Lett. 1995;369(1):57-61.
90. Meinkoth JL, Alberts AS, Went W, Fantozzi D, Taylor SS, Hagiwara M, Montminy M, Feramisco JR. Signal transduction through the cAMP-dependent protein kinase. Mol Cell Biochem. 1993;127-128:179-186.
91. West AE, Chen WG, Dalva MB, Dolmetsch RE, Kornhauser JM, Shaywitz AJ, Takasu MA, Tao X, Greenberg ME. Calcium regulation of neuronal gene expression. Proc Natl Acad Sci U S A. 2001;98(20):11024-11031.
92. Czyzyk TA, Sikorski MA, Yang L, McKnight GS. Disruption of the RII? subunit of PKA reverses the obesity syndrome of Agouti lethal yellow mice. Proc Natl Acad Sci U S A. 2008;105(1):276-281.
93. Kiss RS, Maric J, Ma rcel YL. Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux. J Lipid Res. 2005;46(9):1877-1887.
94. Zhang Y, McGillicuddy FC, Hinkle CC, O'Neill S, Glick JM, Rothblat GH, Reilly MP. Adipocyte modulation of high-density lipoprotein cholesterol. Circulation. 2010;121(11):1347-1355.
95. Nakane T, Hayashibe H, Nakazawa S. An MCA/MR syndrome with hypocholesterolemia due to familial hypobetalipoproteinemia: report of a second patient with Nguyen syndrome. Am J Med Genet A. 2005;137A(3):305-307.
96. Vyroubal P, Chiarla C, Giovannini I, Hyspler R, Ticha A, Hrnciarikova D, Zadak Z. Hypocholesterolemia in clinically serious conditions--review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008;152(2):181-189.
97. Iqbal J, Hussain MM. Intestinal lipid absorption. Am J Physiol Endocrinol Metab. 2009;296(6):E1183-1194.
98. Calvert GD, Abbey M. Plasma lipoproteins, apolipoproteins, and proteins concerned with lipid metabolism. Adv Clin Chem. 1985;24:217-298.
99. Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999;99(16):2192-2217.
100. Schaefer EJ, Eisenberg S, Levy RI. Lipoprotein apoprotein metabolism. J Lipid Res. 1978;19(6):667-687.
101. Glass CK, Witztum JL. Atherosclerosis: the road ahead. Cell. 2001;104(4):503-516.
102. Swan HJ. Mechanical function of the heart and its alteration during myocardial ischemia and infarction. Specific reference to coronary atherosclerosis. Circulation. 1979;60(7):1587-1592.
103. Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868-874.
104. Lusis AJ. Atherosclerosis. Nature. 2000;407(6801):233-241.
105. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997;96(5):1432-1437.
106. Bonithon-Kopp C, Touboul PJ, Berr C, Leroux C, Mainard F, Courbon D, Ducimeti?嫫e P. Relation of intima-media thickness to atherosclerotic plaques in carotid arteries. The Vascular Aging (EVA) Study. Arterioscler Thromb Vasc Biol. 1996;16(2):310-316.
107. Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD. Cholesterol reduction yields clinical benefit: impact of statin trials. Circulation. 1998.;97(10):946-952.
108. Furberg CD, Adams HP Jr, Applegate WB, Byington RP, Espeland MA, Hartwell T, Hunninghake DB, Lefkowitz DS, Probstfield J, Riley WA, Young,B. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation. 1994;90(4):1679-1687.
109. Li AC, Glass CK. The macrophage foam cell as a target for therapeutic intervention. Nat Med. 2002;8(11):1235-1242.
110. Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, Rhee JS, Silverstein R, Hoff HF, Freeman MW. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002;277(51):49982-49988.
111. 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.
112. Witztum JL. You are right too! J Clin Invest. 2005;115(8):2072-2075.
113. Van Eck M, Bos IS, Hildebrand RB, Van Rij BT, Van Berkel TJ. Dual role for scavenger receptor class B, type I on bone marrow-derived cells in atherosclerotic lesion development. Am J Pathol. 2004;165(3):785-794.
114. Joyce CW, Amar MJ, Lambert G, Vaisman BL, Paigen B, Najib-Fruchart J, Hoyt RF Jr, Neufeld ED, Remaley AT, Fredrickson DS, Brewer HB Jr, Santamarina-Fojo S. The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout mice. Proc Natl Acad Sci U S A. 2002;99(1):407-412.
115. Out R, Hoekstra M, Hildebrand RB, Kruit JK, Meurs I, Li Z, Kuipers F, Van Berkel TJ, Van Eck M. Macrophage ABCG1 deletion disrupts lipid homeostasis in alveolar macrophages and moderately influences atherosclerotic lesion development in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 2006;26(10):2295-2300.
116. Whitman SC, Kurowska EM, Manthey JA, Daugherty A. Nobiletin, a citrus flavonoid isolated from tangerines, selectively inhibits class A scavenger receptor-mediated metabolism of acetylated LDL by mouse macrophages. Atherosclerosis. 2005;178(1):25-32.
117. Xia M, Hou M, Zhu H, Ma J, Tang Z, Wang Q, Li Y, Chi D, Yu X, Zhao T, Han P, Xia X, Ling W. Anthocyanins induce cholesterol efflux from mouse peritoneal macrophages: the role of the peroxisome proliferator-activated receptor ??liver X receptor ??ABCA1 pathway. J Biol Chem. 2005;280(44):36792-36801.
118. Osto E, Kouroedov A, Mocharla P, Akhmedov A, Besler C, Rohrer L, von Eckardstein A, Iliceto S, Volpe M, L?卲cher TF, Cosentino F. Inhibition of protein kinase C? prevents foam cell formation by reducing scavenger receptor A expression in human macrophages. Circulation. 2008;118(21):2174-2182.
119. Kao ES, Tseng TH, Lee HJ, Chan KC, Wang CJ. Anthocyanin extracted from Hibiscus attenuate oxidized LDL-mediated foam cell formation involving regulation of CD36 gene. Chem Biol Interact. 2009;179(2-3):212-218.
120. Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B. PPAR-? and PPAR-? activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 2001;7(1):53-58.
121. Yvan-Charvet L, Ranalletta M, Wang N, Han S, Terasaka N, Li R, Welch C, Tall AR. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. J Clin Invest. 2007;117(12):3900-3908.
122. Platt N, Gordon S. Is the class A macrophage scavenger receptor (SR-A) multifunctional? - The mouse's tale. J Clin Invest. 2001;108(5):649-654.
123. de Winther MP, van Dijk KW, Havekes LM, Hofker MH. Macrophage scavenger receptor class A: A multifunctional receptor in atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;20(2):290-297.
124. Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Ueda O, Sakaguchi H, Higashi T, Suzuki T, Takashima Y, Kawabe Y, Cynshi O, Wada Y, Honda M, Kurihara H, Aburatani H, Doi T, Matsumoto A, Azuma S, Noda T, Toyoda Y, Itakura H, Yazaki Y, Kodama T, et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997;386(6622):292-296.
125. M?驥inen PI, Lappalainen JP, Heinonen SE, Lepp?躪en P, L?鑷teenvuo MT, Aarnio JV, Heikkil? J, Turunen MP, Yl??Herttuala S. Silencing of either SR-A or CD36 reduces atherosclerosis in hyperlipidaemic mice and reveals reciprocal upregulation of these receptors. Cardiovasc Res. 2010;88(3):530-538.
126. de Winther MP, Gijbels MJ, van Dijk KW, van Gorp PJ, suzuki H, Kodama T, Frants RR, Havekes LM, Hofker MH. Scavenger receptor deficiency leads to more complex atherosclerotic lesions in APOE3Leiden transgenic mice. Atherosclerosis. 1999;144(2):315-321.
127. Febbraio M, Hajjar DP, Silverstein RL. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest. 2001;108(6):785-791.
128. Nakata A, Nakagawa Y, Nishida M, Nozaki S, Miyagawa J, Nakagawa T, Tamura R, Matsumoto K, Kameda-Takemura K, Yamashita S, Matsuzawa Y. CD36, a novel receptor for oxidized low-density lipoproteins, is highly expressed on lipid-laden macrophages in human atherosclerotic aorta. Arterioscler Thromb Vasc Biol. 1999;19(5):1333-1339.
129. Nozaki S, Kashiwagi H, Yamashita S, Nakagawa T, Kostner B, Tomiyama Y, Nakata A, Ishigami M, Miyagawa J, Kameda-Takemura K, et al. Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects. J Clin Invest. 1995;96(4):1859-1865.
130. 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.
131. Han J, Hajjar DP, Febbraio M, Nicholson AC.Native and modified low density lipoproteins increase the functional expression of the macrophage class B scavenger receptor, CD36. J Biol Chem. 1997;272(34):21654-21659.
132. Nicholson AC. Expression of CD36 in macrophages and atherosclerosis: the role of lipid regulation of PPAR? signaling. Trends Cardiovasc Med. 2004;14(1):8-12.
133. Febbraio M, Hajjar DP, Silverstein RL. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest. 2001;108(6):785-91.
134. Ibrahimi A, Bonen A, Blinn WD, Hajri T, Li X, Zhong K, Cameron R, Abumrad NA. Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscle, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin. J Biol Chem. 1999 ;274(38):26761-26766.
135. Krieger M. Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest. 2001;108(6):793-797.
136. Trigatti B, Rayburn H, Vi?狒ls M, Braun A, Miettinen H, Penman M, Hertz M, Schrenzel M, Amigo L, Rigotti A, Krieger M. Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc Natl Acad Sci U S A. 199;96(16):9322-9327.
137. Gong M, Wilson M, Kelly T, Su W, Dressman J, Kincer J, Matveev SV, Guo L, Guerin T, Li XA, Zhu W, Uittenbogaard A, Smart EJ. HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner. J Clin Invest. 2003;111(10):1579-1587.
138. Gu X, Kozarsky K, Krieger M. Scavenger receptor class B, type I-mediated [3H]cholesterol efflux to high and low density lipoproteins is dependent on lipoprotein binding to the receptor. J Biol Chem. 2000;275(39):29993-30001.
139. Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH, Tall AR, Rader DJ. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest. 2007;117(8):2216-2224.
140. Yokoyama S. Assembly of high-density lipoprotein. Arterioscler Thromb Vasc Biol. 2006;26(1):20-27.
141. Oram JF, Vaughan AM. ATP-Binding cassette cholesterol transporters and cardiovascular disease. Circ Res. 2006;99(10):1031-1043.
142. Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, Yu L, Brewer C, Collins JA, Molhuizen HO, Loubser O, Ouelette BF, Fichter K, Ashbourne-Excoffon KJ, Sensen CW, Scherer S, Mott S, Denis M, Martindale D, Frohlich J, Morgan K, Koop B, Pimstone S, Kastelein JJ, Genest J Jr, Hayden MR. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet. 1999;22(4):336-345.
143. Zhao Y, Pennings M, Hildebrand RB, Ye D, Calpe-Berdiel L, Out R, Kjerrulf M, Hurt-Camejo E, Groen AK, Hoekstra M, Jessup W, Chimini G, Van Berkel TJ, Van Eck M. Enhanced foam cell formation, atherosclerotic lesion development, and inflammation by combined deletion of ABCA1 and SR-BI in bone marrow-derived cells in LDL receptor knockout mice on western-type diet. Circ Res. 2010;107(12):e20-31.
144. Yvan-Charvet L, Ranalletta M, Wang N, Han S, Terasaka N, Li R, Welch C, Tall AR. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. J Clin Invest. 2007;117(12):3900-3908.
145. Singaraja RR, Fievet C, Castro G, James ER, Hennuyer N, Clee SM, Bissada N, Choy JC, Fruchart JC, McManus BM, Staels B, Hayden MR. Increased ABCA1 activity protects against atherosclerosis. J Clin Invest. 2002 ;110(1):35-42.
146. Wang N, Tall AR. Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol. 2003;23(7):1178-1184.
147. Schmitz G, Langmann T. Transcriptional regulatory networks in lipid metabolism control ABCA1 expression. Biochim Biophys Acta. 2005;1735(1):1-19.
148. Martinez LO, Agerholm-Larsen B, Wang N, Chen W, Tall AR. Phosphorylation of a pest sequence in ABCA1 promotes calpain degradation and is reversed by ApoA-I. J Biol Chem. 2003;278(39):37368-37374.
149. Wang N, Chen W, Linsel-Nitschke P, Martinez LO, Agerholm-Larsen B, Silver DL, Tall AR. A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-I. J Clin Invest. 2003;111(1):99-107.
150. Nonomura K, Arai Y, Mitani H, Abe-Dohmae S, Yokoyama S. Insulin down-regulates specific activity of ATP-binding cassette transporter A1 for high density lipoprotein biogenesis through its specific phosphorylation. Atherosclerosis. 2011;216(2):334-341.
151. Jin S, Mathis AS, Rosenblatt J, Minko T, Friedman GS, Gioia K, Serur DS, Knipp GT. Insights into cyclosporine A-induced atherosclerotic risk in transplant recipients: macrophage scavenger receptor regulation. Transplantation. 2004;77(4):497-504.
152. Haidar B, Denis M, Krimbou L, Marcil M, Genest J Jr. cAMP induces ABCA1 phosphorylation activity and promotes cholesterol efflux from fibroblasts. J Lipid Res. 2002;43(12):2087-2094.
153. See RH, Caday-Malcolm RA, Singaraja RR, Zhou S, Silverston A, Huber MT, Moran J, James ER, Janoo R, Savill JM, Rigot V, Zhang LH, Wang M, Chimini G, Wellington CL, Tafuri SR, Hayden MR. Protein kinase A site-specific phosphorylation regulates ATP-binding cassette A1 (ABCA1)-mediated phospholipid efflux. J Biol Chem. 2002;277:41835-41842.
154. Hu YW, Ma X, Li XX, Liu XH, Xiao J, Mo ZC, Xiang J, Liao DF, Tang CK. Eicosapentaenoic acid reduces ABCA1 serine phosphorylation and impairs ABCA1-dependent cholesterol efflux through cyclic AMP/protein kinase A signaling pathway in THP-1 macrophage-derived foam cells. Atherosclerosis. 2009;204(2):35-43.
155. Ma L, Dong F, Denis M, Feng Y, Wang MD, Zha X. Ht31, a protein kinase A anchoring inhibitor, induces robust cholesterol efflux and reverses macrophage foam cell formation through ATP-binding cassette transporter A1. J Biol Chem. 2011;286(5):3370-3378.
156. Hasegawa K, Wakino S, Kanda T, Yoshioka K, Tatematsu S, Homma K, Takamatsu I, Sugano N, Hayashi K. Divergent action of calcium channel blockers on ATP-binding cassette protein expression. J Cardiovasc Pharmacol. 2005;46(6):787-793
157. Tano JY, Vazquez G. Requirement for non-regulated, constitutive calcium influx in macrophage survival signaling. Biochem Biophys Res Commun. 2011;407(2):432-437.
158. Osawa Y, Lee HT, Hirshman CA, Xu D, Emala CW. Lipopolysaccharide-induced sensitization of adenylyl cyclase activity in murine macrophages. Am J Physiol Cell Physiol. 2006;290(1):143-151.
159. Deng T, Zhang L, Ge Y, Lu M, Zheng X. tribution of intracellular calcium and its effect on apoptosis in macrophages: Induction by oxidized LDL. Biomed Pharmacother. 2009;63(4):267-274.
160. Chen JH, Riazy M, Smith EM, Proud CG, Steinbrecher UP, Duronio V. Oxidized LDL-mediated macrophage survival involves elongation factor-2 kinase. Arterioscler Thromb Vasc Biol. 2009;29(1):92-98.
161. Deng TL, Yu L, Ge YK, Zhang L, Zheng XX. Intracellular-free calcium dynamics and F-actin alteration in the formation of macrophage foam cells. Biochem Biophys Res Commun. 2005;338(2):748-756.
162. Li J, Murao K, Imachi H, Masugata H, Iwama H, Tada S, Zhang GX, Kobayashi R, Ishida T, Tokumitsu H. Exendin-4 regulates pancreatic ABCA1 transcription via CaMKK/CaMKIV pathway. J Cell Mol Med. 2010;14(5):1083-1087.
163. Armstrong DL. Calcium channel regulation by calcineurin, a Ca2+-activated phosphatase in mammalian brain. Trends Neurosci. 1989;12(3):117-122.
164. Pallen CJ, Wang JH. A multifunctional calmodulin-stimulated phosphatase. Arch Biochem Biophys. 1985;237(2):281-291
165. Lavialle-Defaix C, Moignot B, Legros C, Lapied B. How does calcium-dependent intracellular regulation of voltage-dependent sodium current increase the sensitivity to the oxadiazine insecticide indoxacarb metabolite decarbomethoxylated JW062 (DCJW) in insect pacemaker neurons? J Pharmacol Exp Ther. 2010;333(1):264-272.
166. Shibasaki F, Hallin U, Uchino H. Calcineurin as a multifunctional regulator. J Biochem. 2002;131(1):1-15.
167. R?伿lmann A, Nordheim A. Effects of the immunosuppressive drugs CsA and FK506 on intracellular signalling and gene regulation. Immunobiology. 1997;198(1-3):192-206.
168. Chueh SC, Kahan BD. Dyslipidemia in renal transplant recipients treated with a sirolimus and cyclosporine-based immunosuppressive regimen: incidence, risk factors, progression, and prognosis. Transplantation. 2003;76(2):375-382.
169. Jardine AG.. Assessing the relative risk of cardiovascular disease among renal transplant patients receiving tacrolimus or cyclosporine. Transpl Int. 2005;18(4):379-384.
170. Le Goff W, Peng DQ, Settle M, Brubaker G, Morton RE, Smith JD. Cyclosporin A traps ABCA1 at the plasma membrane and inhibits ABCA1-mediated lipid efflux to apolipoprotein A-I. Arterioscler Thromb Vasc Biol. 2004;24(11):2155-2161.
171. Iwamoto N, Lu R, Tanaka N, Abe-Dohmae S, Yokoyama S. Calmodulin interacts with ATP binding cassette transporter A1 to protect from calpain-mediated degradation and upregulates high-density lipoprotein generation. Arterioscler Thromb Vasc Biol. 2010;30(7):1446-1452.
172. Wang N, Lan D, Chen W, Matsuura F, Tall AR. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A. 2004;101(26):9774-9779.
173. Kennedy MA, Venkateswaran A, Tarr PT, Xenarios I, Kudoh J, Shimizu N, Edwards PA. Characterization of the human ABCG1 gene: liver X receptor activates an internal promoter that produces a novel transcript encoding an alternative form of the protein. J Biol Chem. 2001;276(42):39438-39447.
174. Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 2009;35(1):57-68.
175. Tai MC, Tsang SY, Chang LY, Xue H. Therapeutic potential of wogonin: a naturally occurring flavonoid. CNS Drug Rev. 2005;11(2):141-150.
176. Gao Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta. 1999;1472(3):643-650.
177. van Leyen K, Kim HY, Lee SR, Jin G, Arai K, Lo EH. Baicalein and 12/15-lipoxygenase in the ischemic brain. Stroke. 2006;37(12):3014-3018.
178. Woo KJ, Lim JH, Suh SI, Kwon YK, Shin SW, Kim SC, Choi YH, Park JW, Kwon TK. Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBP? DNA-binding activity. Immunobiology. 2006;211(5):359-368.
179. Lee JH, Li YC, Ip SW, Hsu SC, Chang NW, Tang NY, Yu CS, Chou ST, Lin SS, Lino CC, Yang JS, Chung JG. The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria- and caspase-3-dependent pathway. Anticancer Res. 2008;28(3A):1701-1711.
180. Leung HW, Yang WH, Lai MY, Lin CJ, Lee HZ. Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis. Food Chem Toxicol. 2007;45(3):403-411.
181. Pidgeon GP, Kandouz M, Meram A, Honn KV. Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells. Cancer Res. 2002;62(9):2721-2727.
182. Sun H, Che QM, Zhao X, Pu XP. Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats. Eur J Pharmacol. 2010;631(1-3):53-60.
183. Madsen L, Petersen RK, S?廨ensen MB, J?廨gensen C, Hallenborg P, Pridal L, Fleckner J, Amri EZ, Krieg P, Furstenberger G, Berge RK, Kristiansen K. Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process. Biochem J. 2003;375(Pt 3):539-549.
184. Liu LL, Gong LK, Wang H, Xiao Y, Wu XF, Zhang YH, Xue X, Qi XM, Ren J. Baicalin inhibits macrophage activation by lipopolysaccharide and protects mice from endotoxin shock. Biochem Pharmacol. 2008;75(4):914-922.
185. Shieh DE, Cheng HY, Yen MH, Chiang LC, Lin CC. Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines. Am J Chin Med. 2006;34(2):245-261.
186. Chang WH, Chen CH, Lu FJ. Different effects of baicalein, baicalin and wogonin on mitochondrial function, glutathione content and cell cycle progression in human hepatoma cell lines. Planta Med. 2002;68(2):128-132.
187. Lee H, Kang R, Hahn Y, Yang Y, Kim SS, Cho SH, Chung SI, Yoon Y. Antiobesity effect of baicalin involves the modulations of proadipogenic and antiadipogenic regulators of the adipogenesis pathway. Phytother Res. 2009;23(11):1615-1623.
188. Guo HX, Liu DH, Ma Y, Liu JF, Wang Y, Du ZY, Wang X, Shen JK, Peng HL. Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet. Acta Pharmacol Sin. 2009;30(11):1505-1512.
189. Waisundara VY, Siu SY, Hsu A, Huang D, Tan BK. Baicalin upregulates the genetic expression of antioxidant enzymes in Type-2 diabetic Goto-Kakizaki rats. Life Sci. 2011;88(23-24):1016-1025.
190. Huang WH, Lee AR, Yang CH. Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Biosci Biotechnol Biochem. 2006;70(10):2371-2380.
191. Himeji M, Ohtsuki T, Fukazawa H, Tanaka M, Yazaki S, Ui S, Nishio K, Yamamoto H, Tasaka K, Mimura A. Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell. Cancer Lett. 2007;245(1-2):269-274.
192. Gao Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta. 1999 ;1472(3):643-650.
193. Zhao Y, Li H, Gao Z, Gong Y, Xu H. Effects of flavonoids extracted from Scutellaria baicalensis Georgi on hemin-nitrite-H2O2 induced liver injury. Eur J Pharmacol. 2006 ;536(1-2):192-199.
194. Cho J, Lee HK. Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells. Eur J Pharmacol. 2004;485(1-3):105-110.
195. Chang WS, Lee YJ, Lu FJ, Chiang HC. Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res. 1993;13(6A):2165-2170.
196. Liu XF, Liu ML, Iyanagi T, Legesse K, Lee TD, Chen SA. Inhibition of rat liver NAD(P)H:quinone acceptor oxidoreductase (DT-diaphorase) by flavonoids isolated from the Chinese herb scutellariae radix (Huang Qin). Mol Pharmacol. 1990;37(6):911-915.
197. Chung H, Jung YM, Shin DH, Lee JY, Oh MY, Kim HJ, Jang KS, Jeon SJ, Son KH, Kong G. Anticancer effects of wogonin in both estrogen receptor-positive and -negative human breast cancer cell lines in vitro and in nude mice xenografts. Int J Cancer. 2008;122(4):816-822.
198. Wang W, Guo Q, You Q, Zhang K, Yang Y, Yu J, Liu W, Zhao L, Gu H, Hu Y, Tan Z, Wang X. Involvement of bax/bcl-2 in wogonin-induced apoptosis of human hepatoma cell line SMMC-7721. Anticancer Drugs. 2006;(7)17:797-805.
199. Wang W, Guo QL, You QD, Zhang K, Yang Y, Yu J, Liu W, Zhao L, Gu HY, Hu Y, Tan Z, Wang XT. The anticancer activities of wogonin in murine sarcoma S180 both in vitro and in vivo. Biol Pharm Bull. 2006;29(6):1132-1137.
200. Baumann S, Fas SC, Giaisi M, M?刜ler WW, Merling A, G?刜ow K, Edler L, Krammer PH, Li-Weber M. Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLC??- and Ca2+-dependent apoptosis. Blood. 2008;111(4):2354-2363.
201. Montero M, Lobat?曝 CD, Hern?鴨dez-Sanmiguel E, Santodomingo J, Vay L, Moreno A, Alvarez J. Direct activation of the mitochondrial calcium uniporter by natural plant flavonoids. Biochem J. 2004;384(Pt 1):19-24.
202. Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science. 1999;284(5412):339-343.
203. Springer JE, Azbill RD, Nottingham SA, Kennedy SE. Calcineurin-mediated BAD dephosphorylation activates the caspase-3 apoptotic cascade in traumatic spinal cord injury. J Neurosci. 2000;20(19):7246-7251.
204. Chi YS, Cheon BS, Kim HP. Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells. Biochem Pharmacol. 2001;61(10):1195-1203.
205. Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochem Pharmacol. 1999;58(5):759-765.
206. Chen YC, Shen SC, Chen LG, Lee TJ, Yang LL. Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide. Biochem Pharmacol. 2001;61(11):1417-1427.
207. Piao HZ, Choi IY, Park JS, Kim HS, Cheong JH, Son KH, Jeon SJ, Ko KH, Kim WK. Wogonin inhibits microglial cell migration via suppression of nuclear factor-?羠 activity. Int Immunopharmacol. 2008;8(12):1658-1662.
208. Lee BS, Shim SM, Heo J, Pae HO, Seo BY, Han SY, Sohn DH, Jang SI, Chung HT. Wogonin suppresses TARC expression induced by mite antigen via heme oxygenase 1 in human keratinocytes. Suppressive effect of wogonin on mite antigen-induced TARC expression. J Dermatol Sci. 2007;46(1):31-40.
209. Lim H, Kim HP. Inhibition of mammalian collagenase, matrix metalloproteinase-1, by naturally-occurring flavonoids. Planta Med. 2007;73(12):1267-1274.
210. Chang YL, Shen JJ, Wung BS, Cheng JJ, Wang DL. Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Mol Pharmacol. 2001;60(3):507-513.
211. Lin CM, Chang H, Chen YH, Li SY, Wu IH, Chiu JH. Protective role of wogonin against lipopolysaccharide-induced angiogenesis via VEGFR-2, not VEGFR-1. Int Immunopharmacol. 2006;6(11):1690-1698.
212. Lee SO, Jeong YJ, Yu MH, Lee JW, Hwangbo MH, Kim CH, Lee IS. Wogonin suppresses TNF-??induced MMP-9 expression by blocking the NF-?羠 activation via MAPK signaling pathways in human aortic smooth muscle cells. Biochem Biophys Res Commun. 2006;351(1):118-125.
213. Chi YS, Lim H, Park H, Kim HP. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochem Pharmacol. 2003;66(7):1271-1278.
214. Lim BO. Efficacy of wogonin in the production of immunoglobulins and cytokines by mesenteric lymph node lymphocytes in mouse colitis induced with dextran sulfate sodium. Biosci Biotechnol Biochem. 2004;68(12):2505-2511.
215. Hui KM, Huen MS, Wang HY, Zheng H, Sigel E, Baur R, Ren H, Li ZW, Wong JT, Xue H. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochem Pharmacol. 2002;64(9):1415-1424.
216. Qi Q, Peng J, Liu W, You Q, Yang Y, Lu N, Wang G, Guo Q. Toxicological studies of wogonin in experimental animals. Phytother Res. 2009;23(3):417-422.
217. Peng J, Qi Q, You Q, Hu R, Liu W, Feng F, Wang G, Guo Q. Subchronic toxicity and plasma pharmacokinetic studies on wogonin, a natural flavonoid, in Beagle dogs. J Ethnopharmacol. 2009;124(2):257-262.
218. Efferth T, Fu YJ, Zu YG, Schwarz G, Konkimalla VS, Wink M. Molecular target-guided tumor therapy with natural products derived from traditional Chinese medicine. Curr Med Chem. 2007;14(19):2024-2032.
219. Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. 2008;8(7):634-646.
220. Bose M, Lambert JD, Ju J, Reuhl KR, Shapses SA, Yang CS. The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice. J Nutr. 2008;138(9):1677-1683.
221. Murosaki S, Lee TR, Muroyama K, Shin ES, Cho SY, Yamamoto Y, Lee SJ. A combination of caffeine, arginine, soy isoflavones, and L-carnitine enhances both lipolysis and fatty acid oxidation in 3T3-L1 and HepG2 cells in vitro and in KK mice in vivo. J Nutr. 2007;137(10):2252-2257.
222. Rayalam S, Della-Fera MA, Yang JY, Park HJ, Ambati S, Baile CA. Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes. J Nutr. 2007;137(12):2668-2673.
223. Hayek T, Fuhrman B, Vaya J, Rosenblat M, Belinky P, Coleman R, Elis A, Aviram M. Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. Arterioscler Thromb Vasc Biol. 1997;17(11):2744-2752.
224. Fuhrman B, Aviram M. Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr Opin Lipidol. 2001;12(1):41-48.
225. Gautam R, Jachak SM. Recent developments in anti-inflammatory natural products. Med Res Rev. 2009;29(5):767-820.
226. Moon YJ, Wang X, Morris ME. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro. 2006;20(2):187-210.
227. Huang Y, Tsang SY, Yao X, Chen ZY. Biological properties of baicalein in cardiovascular system. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5(2):177-184.
228. Ma Z, Otsuyama K, Liu S, Abroun S, Ishikawa H, Tsuyama N, Obata M, Li FJ, Zheng X, Maki Y, Miyamoto K, Kawano MM. Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood 2005;105(8):3312-3318.
229. Hsieh YC, Hsieh SJ, Chang YS, Hsueh CM, Hsu SL. The lipoxygenase inhibitor, baicalein, modulates cell adhesion and migration by up-regulation of integrins and vinculin in rat heart endothelial cells. Br J Pharmacol. 2007;151(8):1235-1245.
230. Cheng LC, Su KH, Kou YR, Shyue SK, Ching LC, Yu YB, Wu YL, Pan CC, Lee TS. ??Lipoic acid ameliorates foam cell formation via liver X receptor α-dependent upregulation of ATP-binding cassette transporters A1 and G1. Free Radic Biol Med. 2011;50(1):47-54.
231. Yamauchi Y, Hayashi M, Abe-Dohmae S, Yokoyama S. Apolipoprotein A-I activates protein kinase C ? signaling to phosphorylate and stabilize ATP binding cassette transporter A1 for the high density lipoprotein assembly. J Biol Chem. 2003;278(48):47890-47897.
232. Wang Y, Oram JF. Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a phospholipase D2 pathway. J Biol Chem. 2005;280(43):35896-36903.
233. Wang Y, Oram JF. Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a protein kinase C ? pathway. J Lipid Res. 2007;48(5):1062-1068.
234. Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y, Tsuneyama K, Nagai Y, Takatsu K, Urakaze M, Kobayashi M, Tobe K. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes. 2009;58(11):2574-2582
235. Blad? C, Arola L, Salvad? MJ. Hypolipidemic effects of proanthocyanidins and their underlying biochemical and molecular mechanisms. Mol Nutr Food Res. 2010;54(1):37-59.
236. Naaz A, Yellayi S, Zakroczymski MA, Bunick D, Doerge DR, Lubahn DB, Helferich WG, Cooke PS. The soy isoflavone genistein decreases adipose deposition in mice. Endocrinology. 2003;144(8):3315-3320.
237. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression. J Nutr. 2000;130(12):3122S-3126S.
238. Harmon AW, Harp JB. Differential effects of flavonoids on 3T3-L1 adipogenesis and lipolysis. Am J Physiol Cell Physiol. 2001;280(4):C807-813.
239. Margareto J, Larrarte E, Marti A, Martinez JA. Up-regulation of a thermogenesis-related gene (UCP1) and down-regulation of PPAR? and aP2 genes in adipose tissue: possible features of the antiobesity effects of a ??-adrenergic agonist. Biochem Pharmacol. 2001;61(12):1471-1478.
240. Sakaue H, Ogawa W, Matsumoto M, Kuroda S, Takata M, Sugimoto T, Spiegelman BM, Kasuga M. Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase. J Biol Chem. 1998;273(44):28945-28952.
241. Margareto J, Larrarte E, Marti A, Martinez JA. Up-regulation of a thermogenesis-related gene (UCP1) and down-regulation of PPAR? and aP2 genes in adipose tissue: possible features of the antiobesity effects of a ??-adrenergic agonist. Biochem Pharmacol. 2001;61(12):1471-1478.
242. Sakaue H, Ogawa W, Matsumoto M, Kuroda S, Takata M, Sugimoto T, Spiegelman BM, Kasuga M. Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase. J Biol Chem. 1998;273(44):28945-28952.
243. Ahmadian M, Wang Y, Sul HS. Lipolysis in adipocytes. Int J Biochem Cell Biol. 2010;42(5):555-559.
244. Mori S, Satou M, Kanazawa S, Yoshizuka N, Hase T, Tokimitsu I, Takema Y, Nishizawa Y, Yada T. Body fat mass reduction and up-regulation of uncoupling protein by novel lipolysis-promoting plant extract. Int J Biol Sci. 2009;5(4):311-318.
245. Han LK, Sumiyoshi M, Zhang J, Liu MX, Zhang XF, Zheng YN, Okuda H, Kimura Y. Anti-obesity action of Salix matsudana leaves (Part 1). Anti-obesity action by polyphenols of Salix matsudana in high fat-diet treated rodent animals. Phytother Res. 2003;17(10):1188-1194.
246. Saito T, Abe D, Sekiya K. Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2007;357(2):371-376.
247. Cummings DE, Brandon EP, Planas JV, Motamed K, Idzerda RL, McKnight GS. Genetically lean mice result from targeted disruption of the RII? subunit of protein kinase A. Nature. 1996;382(6592):622-626.
248. Planas JV, Cummings DE, Idzerda RL, McKnight GS. Mutation of the RIIbeta subunit of protein kinase A differentially affects lipolysis but not gene induction in white adipose tissue. J Biol Chem. 1999;274(51):36281-36287.
249. Schreyer SA, Cummings DE, McKnight GS, LeBoeuf RC. Mutation of the RII? subunit of protein kinase A prevents diet-induced insulin resistance and dyslipidemia in mice. Diabetes. 2001;50(11):2555-2562.
250. Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem. 2004;50(9):1511-1525.
251. Li AC, Binder CJ, Gutierrez A, Brown KK, Plotkin CR, Pattison JW, Valledor AF, Davis RA, Willson TM, Witztum JL, Palinski W, Glass CK. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPAR?? ???? and ?? J Clin Invest. 2004;114(11):1564-1576.
252. Zou Y, Lu Y, Wei D. Hypocholesterolemic effects of a flavonoid-rich extract of Hypericum perforatum L. in rats fed a cholesterol-rich diet. J Agric Food Chem. 2005;53(7):2462-2466.
253. Xu G, Watanabe T, Iso Y, Koba S, Sakai T, Nagashima M, Arita S, Hongo S, Ota H, Kobayashi Y, Miyazaki A, Hirano T. Preventive effects of heregulin-?? on macrophage foam cell formation and atherosclerosis. Circ Res. 2009;105(5):500-510.
254. Terra X, Fern?鴨dez-Larrea J, Pujadas G, Ard?嫛ol A, Blad? C, Salvad? J, Arola L, Blay M. Inhibitory effects of grape seed procyanidins on foam cell formation in vitro. J Agric Food Chem. 2009;57(6):2588-2594.
255. Berrougui H, Grenier G, Loued S, Drouin G, Khalil A. A new insight into resveratrol as an atheroprotective compound: inhibition of lipid peroxidation and enhancement of cholesterol efflux. Atherosclerosis. 2009;207(2):420-427.
256. Hu XT, Ford K, White FJ. Repeated cocaine administration decreases calcineurin (PP2B) but enhances DARPP-32 modulation of sodium currents in rat nucleus accumbens neurons. Neuropsychopharmacology. 2005;30(5):916-926.
257. Rakhilin SV, Olson PA, Nishi A, Starkova NN, Fienberg AA, Nairn AC, Surmeier DJ, Greengard P. A network of control mediated by regulator of calcium/calmodulin-dependent signaling. Science. 2004;306(5696):698-701.
258. West AE, Chen WG, Dalva MB, Dolmetsch RE, Kornhauser JM, Shaywitz AJ, Takasu MA, Tao X, Greenberg ME. Calcium regulation of neuronal gene expression. Proc Natl Acad Sci U S A. 2001;98(20):11024-11031.
259. Arakawa R, Yokoyama S. Helical apolipoproteins stabilize ATP-binding cassette transporter A1 by protecting it from thiol protease-mediated degradation. J Biol Chem. 2002;277(25):22426-22429.
260. Arakawa R, Tsujita M, Iwamoto N, Ito-Ohsumi C, Lu R, Wu CA, Shimizu K, Aotsuka T, Kanazawa H, Abe-Dohmae S, Yokoyama S. Pharmacological inhibition of ABCA1 degradation increases HDL biogenesis and exhibits antiatherogenesis. J Lipid Res. 2009;50(11):2299-2305.
261. Lee TS, Lin CY, Tsai JY, Wu YL, Su KH, Lu KY, Hsiao SH, Pan CC, Kou YR, Hsu YP, Ho LT. Resistin increases lipid accumulation by affecting class A scavenger receptor, CD36 and ATP-binding cassette transporter-A1 in macrophages. Life Sci. 2009;84(3-4):97-104.