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研究生:何國彰
研究生(外文):Kuo-Jang Ho
論文名稱:(1)腐植酸毒理機制之研究;(2)中藥厚朴純化物Honokiol的抗癌機制探討
論文名稱(外文):(1)Study on the Toxic Mechanism of Humic Acid; (2)Study on the Mechanism of Honokiol-induced Apoptosis
指導教授:呂鋒洲呂鋒洲引用關係
指導教授(外文):Fung-Jou Lu
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生物化學暨分子生物學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:160
中文關鍵詞:腐植酸氧化壓力大骨節病成骨細胞細胞計畫性死亡
外文關鍵詞:humic acidironoxidative stressKashin-Beck diseaseosteoblastapoptosis
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(一)
腐植酸已經被認為對許多哺乳類細胞具有毒性,但是至今為止還不知道腐植酸對於細胞特有的毒理機制。在本實驗裡,我們分析腐植酸的氧化還原性質,發現了腐植酸可以在水溶液的環境底下將三價鐵離子還原成二價的形式,而且在酸鹼值4.0到9.0之間都具有這種還原能力。利用thiobarbituric acid-reactive substances當作脂質過氧化的指標來分析腐植酸對於亞麻油酸以及老鼠肝臟細胞的微粒體的作用,結果發現腐植酸明顯的造成亞麻油酸以及老鼠肝臟細胞的微粒體產生脂質過氧化作用。若是同時加入單線態氧的清除劑sodium azide或是超氧自由基清除劑disodium 4,5-dihydroxy-1,3-benzene-disulfonic acid可以部分的抑制腐植酸造成的脂質過氧化作用,這說明了單線態氧以及超氧自由基涉及了腐植酸誘導脂質產生過氧化反應的過程。由superoxide dismutase-inhibitable cytochrome c reduction assay實驗中發現,腐植酸在此反應系統中可以產生超氧自由基,且超氧自由基產生的速率也會隨著腐植酸的濃度增加而上升。除此之外,腐植酸同樣也會造成鐵蛋白中的鐵離子由三價形式還原成二價,並且從鐵蛋白質中釋放出來,而此作用可被超氧自由基清除劑抑制。從鐵蛋白釋放出來的鐵離子具有加速腐植酸對於脂質所產生的過氧化作用。綜合我們實驗的結果,我們證明腐植酸可以將鐵蛋白中的鐵離子還原,並且從鐵蛋白質中釋放出來,釋放出來的鐵離子加速了腐植酸所產生的脂質過氧化作用。因此,腐植酸以及被釋放出來的鐵離子會擾亂氧化還原狀態的平衡,並且在生物系統內產生了氧化壓力。此結果可能是腐植酸最重要的細胞毒理機制。
(二)
大骨節病主要發生在中國大陸地區,它是一種地方退化性的骨關節疾病,此疾病主要病徵是病人會有嚴重的骨頭變形以及身材較正常人矮小。根據流行病學的調查,有證據顯示出患區低硒食物與飲用水中的高量黃腐酸及腐植酸是造成大骨節病主要的致病因子。由我們的實驗結果可以發現,處理腐質酸會造成老鼠骨母細胞存活度下降;若細胞前處理抗氧化物質glutathione monoethyl ester (GSH-ME)或N-acetylcysteine (NAC)後,則腐質酸對細胞的傷害會減輕。經由流式細胞技術的分析結果發現,腐植酸會造成細胞膜脂質過氧化反應的發生以及細胞內活性氧物質的上升,其中包括過氧化氫、超氧自由基與一氧化氮。此外,腐植酸也會明顯地造成細胞內粒線體膜電位與質量的下降,導致細胞停滯在細胞週期G0/G1 時期;同時也會造成細胞內還原形GSH以及NADPH濃度下降。老鼠骨母細胞處理腐質酸24小時後,可造成細胞內酵素glutathione peroxidase (GPX)、glutathione reductase (GR) 、glucose-6 phosphate dehydrogenase (G6PDH)、phase I biotransfromation enzyme cytochrome P450 reductase (CPR),以及phase II biotransfromation enzymes NAD(P)H: quinone oxidoreductase(NQR) 及glutathione-s transferase (GST)活性下降;利用了Fura-2 AM來偵測細胞內鈣離子濃度的變化,腐植酸會造成細胞內鈣離子的上升,並且證明了鈣離子是由細胞外進入的。若細胞前處理BAPTA-AM (acetoxmethyl-1,2-Bis(2-Aminophenoxy)ethane N,N,N′,N′-tetraaceticacid)三十分鐘,也可以減輕腐質酸對細胞的傷害。本研究結果證明腐植酸可以產生活性氧物種以及抑制細胞內抗氧化系統的活性,這是造成骨母細胞細胞內的氧化壓力上升原因之一,這些說明腐植酸在大骨節病的致病機轉中可能扮演重要的角色。
(三)
目前對於血癌的化學治療,最有效的方法就是誘導腫瘤細胞產生細胞計劃性死亡。Honokiol是由中藥厚朴(Magnolia officnalis)樹皮中萃取出來的一種純物質,在本篇的研究中,我們發現honokiol可以抑制人類血癌細胞HL-60與Jurkat cells的生長,並使得細胞產生計劃性死亡。然而,濃度為50 M的honokiol對於人類neutrophils與PBMC並不會產生任何的細胞毒性。Honokiol會使細胞產生低於二倍體的DNA,造成細胞內DNA呈階梯狀式斷裂;也會使得細胞膜內的脂質phosphatidylserine向外翻出,並且活化多種的caspases,造成poly (ADP-ribose) polymerase (PARP)的裂解。利用螢光的方法偵測caspases的活性,我們發現honokiol可以活化caspase-3、 -2以及 -9的活性。此外,honokiol也能使粒線體內的cytochrome c釋出至細胞質,並且造成粒線體膜電位(mitochondrial transmembrane potential)與膜內pH下降。前處理caspase抑制劑z-Val-Ala-Asp-floromethylketone (zVAD-fmk)可以完全地抑制honokiol引起的細胞計劃性死亡,而其他的caspase (caspase-3、 -2、 -6以及 -9)抑制劑也同樣都有抑制的效果。這個結果說明了honokiol是以活化多種caspase的形式來產生細胞計劃性死亡的訊息。綜合以上的結果,我們證明了honokiol能抑制癌細胞的生長,並且引發細胞產生計畫性死亡。其機制是因為honokiol能使粒線體內的cytochrome c釋出至細胞質,造成caspase-3以及 -9的活化,最後導致PARP的裂解以及產生階梯狀斷裂的DNA。我們認為,honokiol引發癌細胞計劃性死亡的作用模式,將成為今後腫瘤細胞進行化學治療時的參考。
(1)
Humic acid (HA) has been shown to be a toxic factor for many mammalian cells, however the specific mechanism of the cytotoxicity induced by HA remains unclear. From the assessment of its redox properties, HA has been shown to be capable of reducing iron(III) to iron(II) in aqueous conditions over a broad range of pH values (from 4.0 to 9.0). By using thiobarbituric acid-reactive substances as an index, the presence of HA was noted to increase the extent of lipid peroxidation both for linoleic acids and within rat liver microsomes. In addition, the increase in HA-induced lipid peroxidation is partially inhibited by sodium azide (NaN3, a singlet oxygen scavenger) or disodium 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron, a superoxide scavenger), reflecting the involvement of singlet oxygen and superoxide in the process of lipid peroxidation. The addition of HA into a reaction system has been shown to generate superoxide in a dose-dependent manner by the superoxide dismutase-inhibitable cytochrome c reduction assay. In addition, HA is able to reduce and release iron from ferritin, but this process is partially inhibited by superoxide scavengers. Subsequently, the released iron from ferritin was shown to accelerate the HA-induced lipid peroxidation. Our results conclude that HA has the ability to reduce and release iron from ferritin storage as well as to promote lipid peroxidation. Therefore, HA coupled with released iron can disturb the redox balance and elicit oxidative stress within a biological system. This may be one of the most important mechanisms for HA-induced cytotoxicity.
(2)
Kashin-Beck disease (KBD), which occurs mainly in China, is an endemic, degenerative, osteoarticular disorder associated with severe skeletal deformation and dwarfism. The epidemiology of KBD provides convincing evidence that selenium deficiency in the diet and high content humic acid (HA) in the drinking water are the main causative factors of the disease in China. In the present study, we revealed that the presence of HA was noted to decrease the viability of rat calvaria osteoblasts. However, HA-induced cytotoxicy was partly inhibited by glutathione monoethyl ester (GSH-ME) or N-acetylcysteine (NAC). By the flow cytometry analysis, the addition of HA into osteoblasts has been shown to increase the extent of lipid peroxide and reactive oxygen species, they consisting of hydrogen peroxide, superoxide and nitric oxide. In addition, HA mediated G0/G1 phase arrest and dramatically decreased mitochondrial transmembrane potential as well as mitochondrial mass in rat osteoblasts. In rat calvaria osteoblasts, HA induced significant decreases in the concentration of cellular reduced glutathione and NADPH. The activities of glutathione peroxidase (GPX), glutathione reductase (GR), cytochrome P450 reductase (CPR), NAD(P)H: quinone oxidoreductase (NQR1), glutathione S transferase (GST) and glucose-6 phosphate dehydrogenase (G6PDH) were also decreased following exposure for 24 hr to HA. Cytosolic free Ca2+ levels were recorded by using the Ca2+-sensitive dye Fura-2. Humic acid induced a [Ca2+]i increase at concentrations above 200 nM. The levels of elevated intracellular calcium were sustained and did not return to baseline even after 20 min. This increase of intracellular calcium was suppressed in the presence of EGTA, indicating that the [Ca2+]i rise was due to the entry of extracellular calcium. HA-induced cytotoxicy was also partly inhibited by intracellular calcium chelator, BAPTA-AM [acetoxmethyl-1,2-Bis (2-Aminophenoxy) ethane N,N,N′,N′- tetraacetic acid]. Our results conclude that HA has the ability to inhibit antioxidant enzyme activities and elicit oxidative stress in the cell. This may be one of the most important mechanisms for HA-induced KBD.
(3)
Induction of apoptosis in malignant cells could be an efficient strategy of chemotherapy for leukemia. In the present study, we have demonstrated that honokiol, isolated from the stem bark of Magnolia officnalis, could inhibit the growth in human leukemic HL-60 and Jurkat cells in a dose- and time-dependent manner by inducing apoptosis. However, treatment with 50 M of honokiol for 72 hr showed no cytotoxicity in human neutrophils and PBMC of healthy donors. Apoptosis was determined by following criteria: presence of hypodiploid DNA, internucleosomal DNA fragmentation, phosphatidylserine externalization, cleavage of poly (ADP-ribose) polymerase (PARP), and activation of caspases. Using a fluorogenic assay, it was found that honokiol increased the activities of caspase-3, -2, -6, and -9 in the process of apoptosis. In addition, treatment with honokiol appeared to decline the mitochondrial transmembrane potential and the intracellular pH, as well as increase the release of cytochrome c from mitochondria. By TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-FITC nick end labeling) assay, honokiol-induced apoptosis could be almost completely blocked by z-Val-Ala-Asp-floromethylketone (zVAD-fmk), a broad-spectrum caspase inhibitor, and significantly attenuated by caspase-9, -3 and -2 inhibitors. It is suggested that honokiol-induced apoptotic signaling might be a multiple caspase profile. In conclusion, our results demonstrate that honokiol dramatically suppress cell growth by inducing apoptosis which is triggered by the release of cytochrome c into the cytosol, activation of caspase-9 and caspase-3, degradation of PARP, and DNA fragmentation. The induction of apoptosis by honokiol may provide a pivotal mechanism for its cancer chemopreventive action.
目錄
第一部分 腐植酸毒理機制之研究 ………………………………1
第一章 中文摘要 …………………………………………………2
第二章 英文摘要 …………………………………………………4
第三章 本文 ………………………………………………………7
一、腐植酸誘導氧化壓力作用之探討 ……………………………8
第一節 緒言 ………………………………………………………9
第二節 實驗方法 …………………………………………………13
第三節 實驗結果 …………………………………………………18
第四節 討論 ………………………………………………………24
第五節 參考文獻 …………………………………………………29
第六節 圖表 ………………………………………………………35
二、腐植酸對成骨細胞毒性之研究 ………………………………53
第一節 緒言 ………………………………………………………54
第二節 實驗方法 …………………………………………………60
第三節 實驗結果 …………………………………………………72
第四節 討論 ………………………………………………………80
第五節 參考文獻 …………………………………………………84
第六節 圖表 ………………………………………………………90
第二部分 中藥厚朴純化物Honokiol的抗癌機制探討 …………109
第一章 中文摘要 …………………………………………………110
第二章 英文摘要 …………………………………………………111
第三章 本文 ………………………………………………………112
第一節 緒言 ………………………………………………………113
第二節 實驗方法 …………………………………………………118
第三節 實驗結果 …………………………………………………128
第四節 討論 ………………………………………………………133
第四章 參考文獻…………………………………………………135
第五章 圖表 ………………………………………………………143
發表論文附錄 ………………………………………………………160
(1)
1. Steelink, C. (1963). What is humic acid? J. Chem. Education. 40, 379-384.
2. Hayes, M.H.B. (1989). Humic substances 2. A Wiley-Interscience publication press.
3. Flaig, W. (1966). Chemistry of humic substance in the use of isotopes in soil organic matter studies. Report of FAOIAEA technical meeting, Pergamon, Elmsford, NY, 103-127.
4. Kononova, I.I. (1977). Soil Organic Matter. 405.
5. Kononova, M.M. (1966). Soil Organic Matter. Pergamon, Elmsford, NY, 544.
6. Huffman, J.R.E.W.D. and Stuber H.A. (1985). In Aiken, G.R., Mcknight, D.M., Wershaw, R.L., MacCarthy, P., eds, Humic substances in soil, sediment, and water, John Wiley & Sons, New York, 433-582.
7. Leenheer, J.A. and Noyes, T.I. (1989). In Hayes, M.H.B., MacCarthy, P., Malcolm, R.L., Swift, R.S., eds. Humic substances II, John Wiley & Sons, New York, 257-446.
8. Wilson, M.A., Jones, A.J., Williamson, B. (1978). Nuclear magnetic resonance spectroscopy of humic materials. Nature 276, 487-489.
9. Worobey, B.L., and Webster, G.R.B. (1981). Indigenous 13C-NMR structural features of soil humic substances. Nature 292, 526-529.
10. Stevenson, F.J. (1982). Humus chemistry: Genesis, composition, reaction. New York, Wiley 443.
11. Madhun, Y.A., Freed, V.H., and Young, J.L. (1986). Binding of ionic and neutral herbicide by soil humic acid. Am. J. Soil Sci. 50, 319-322.
12. Peng, A., and Xu, L. (1987). The effects of humic acids on the chemical and biological properties of selenium in the environment. Sci. Total Environ. 64, 305-310.
13. Rex, R.W. (1960). Electron paramagnetic resonance studies of stable free radicals in lignins and humic acids. Nature 188, 1185-1186.
14. Atherton, N.M., Cranwell, P.A., Floyd, A.J., Haworth, R.D. (1967). Humic acid. I. ESR spectra of humic acids. Tetrahedron 23, 1653-1667.
15. Schnitzer, M., Skinner, S.I.M. (1969). Free radicals in soil humic compounds. Soil Sci. 108, 383-390.
16. Szilagyi, M. (1973). The redox properties and the determination of the normal potential of the peat-water system. Soil Sci. 115, 434-441.
17. Skogerbae, R.K. and Wilson, S.A. (1981). Reduction of ionic species by fulvic acid. Anal. Chem. 53, 228-232.
18. Szilagyi, M. (1973). Reduction of Fe3+ ion by humic acid preparations. Soil Sci. 111, 233-238.
19. Loveley, D.R., Coates, J.D., Blunt-Harris, E.L., Phillips, E.J.P., Woodward, J.C. (1996). Humic substances as electron acceptors for microbial respiration. Nature 382, 445-448.
20. Ponka, P., Beaumont, C., Richardson, D.R. (1998). Function and regulation of transferrin and ferritin. Seminar in Hematology 35, 35-54.
21. Ryan, T.P., and Aust. S.D. (1992). The role of iron in oxygen-mediated toxicities. Crit. Rev. Toxicol. 22, 119-141.
22. Darley-Usmar, V., Wiseman, H., and Halliewll, B. (1995). Nitric oxide and oxygen radicals: a question of balance. FEBS Lett. 369, 131-135.
23. Harrison, P.M., and Arosio, P. (1996). The ferritin: molecular properties, iron storage function and cellular regulation. Biochim. Biophys. Acta 1275, 161-203.
24. Reif, D.W. (1992). Ferritin as a source of iron for oxidative damage. Free Rad. Biol. Med. 12, 417-427.
25. Reif, D.W., Samokyszyn, V.M., Miller, D.M., Aust, S.D. (1989). Alloxan- and glutathione-dependent ferritin iron release and lipid peroxidation. Arch. Biochem. Biophys. 269, 407-414.
26. Thomas, C.E., Aust, S.D. (1987). Reductive release of iron from ferritin by cation free radicals of paraquat and other bipyridyl. J. Biol. Chem. 261, 13064-13070.
27. Ahmad, S., Singh, V., Rao, G.S. (1995). Release of iron from ferritin by 1,2,4,-benzenetriol. Chem-Biol. Interact. 96, 103-111.
28. Chiu, H.C., Shih, S.R., Lu, F.J., Yang, H.L. (1993). Stimulation of endothelin production in cultured human endothelial cells by florescent compounds associated with blackfoot disease. Thromb. Res. 69, 139-151.
29. Liang, H.J., Tsai, C.L., Lu, F.J. (1998). Oxidative stress induced by humic acid solvent extraction fraction in cultured rabbit articular chondrocytes. J. Toxicol. Environ. Health 54, 477-489.
30. Liang, H.J., Tsai, C.L., Chen, P.Q., and Lu, F.J. (1999). Oxidative injury induced by synthetic humic acid polymer and monomer in cultured rabbit articular chondrocytes. Life Sci. 65, 1163-1173.
31. Cheng, M.L., Ho, H.Y., Chiu, D.T., Lu, F.J. (1999). Humic acid-mediated oxidative damages to human erythrocytes: A possible mechanism leading to anemia in blackfoot disease. Free Rad. Biol. Med. 27, 470-477.
32. Gaitan, E., Jolly, R.L., Lee, N.E., Lindsay, R.J., Cooksey, R.C., Hill, J.R., and Kelly, K. (1983). Phthalate ester: Possible progoitrogens in water supply of a Colombia district with endemic goiter. J. Am. Chem. Soc. 23, 175-178.
33. Gaitan, E., Medina, T.A., and Zia, M.S. (1980). Goiter prevalence and bacterial contamination of water supply. J. Clin. Endocrinol. Metab. 51, 957-962.
34. Cooksey, R.C., Gaitan, E., Lindsay, R.J., Hill, J.R., and Kelly, K. (1985). Humic substances, a possible source of environmental goitrogens. Org. Geochem. 8, 77-80.
35. Lu, F.J., Guo, H., Chiangs, H.S., and Hong, C.L. (1986). Relationships between the fluorescent intensity of well water and the incidence rate of bladder cancer. J. Chinese Oncol. Soc. 2, 14.
36.Zhai, S.S., Kimbrough, R.D., Meng, B., Han, J.Y., Levoid, M., Hou, X., and Yin, X.N. (1990). Kashin-Beck disease: A cross-sectional study in seven villages in the peoples’ Republic of China. J. Toxicol. Environ. Health. 30, 239-259.
37. Lu, F.J., Tsai, M.H., and Ling, K.H. (1977). Studies on fluorescent compound in drinking water of blackfoot disease endemic area. 1. The toxic effects of fluorescent compound on the chick embryos. J. Formosan Med. Assoc. 76, 58-63.
38. Chen, J.Y., Lu, F.J., and Ling, K.H. (1977). Studies on fluorescent compounds in drinking water of blackfoot disease endemic area. 5. Effects of fluorescent compounds on protein and nucleic acid synthesis in growing HeLa cells. Chinese J. Microbiol. 10, 115-117.
39. Hofmanova, J., Kozubik, A, Hola, J., Soucek, K., Kovarikova, M., and Zadak, Z. (1999). Effects of sodium humate on the cell cycle and proliferation of mammalian cells. Clin. Biochem. Metab. 7, 4-11.
40. Lu, F.J., Tsai, S.C., and Chen, J.Y. (1980). Studies on natural toxicants occurring in artesian well of blackfoot disease endemic area in Taiwan: chromosome aberrations in cultured lymphocytes exposed to fluorescent compounds. J. Chinese Biochem. Soc. 9, 49-45.
41. Ribas, G., Garbonell, E., Creus, A., Xamena, N., and Marcos, R. (1997). Genotoxicity of humic acid in cutured human lymphocytes and its interaction with the herbicides alachlor and maleic hydrazide. Environ. Mol. Mutagenesis 29, 272-276.
42. 劉東明。(1986)。烏腳病區井水中螢光物質之研究:螢光物質對小白鼠肝臟內脂質過氧化反應後醛類產物之影響。台大醫學院生化學研究所碩士論文。
43. 黃蘭如。(1991)。烏腳病區井水中抽取物質對小白鼠肝臟中過氧化體增生之研究。台大醫學院生化學研究所碩士論文。
44. Yang, H.L., Lu, F.J., Wung, S.L., Chiu, H.C. (1994). Humic acid induces expression of tissue factor by cultured endothelial cells: regulation by cytosolic calcium and protein kinase C. Thromb. Haemostas. 71, 325-330.
45. Lu, F.J., Lee, Y.S. (1992). Humic acid: inhibitor of plasmin. Sci. Total Environ. 144, 135-139.
46. Lu, F.J., Shih, S.R., Liu, T.M., and Show, S.H. (1990). The effect of fluorescent humic substances existing in the well water of blackfoot disease endemic area in Taiwan on prothrombin time and activated partial thromplastin time in vitro. Thromb. Res. 57, 747-753.
47. Huang, T.S., Lu, F.J., Chopra, I.J. (1993). Inhibition of hepatic thyroxine 5’-monodeiodinase by humic acids. Environ. Toxicol. Chem. 12, 1267-1271.
48. Lu, F.J., Huang, T.S., and Chen, Y.S. (1994). Effects of humic-acid-metal complexes on hepatic carnitine palmitoyltransferase, carnitine acetyltrnasferase and catalase activities. Environ. Toxicol. Chem. 13, 435-441.
49. Lu, F.J., Liu, T.M. (1986). Fluorescent compounds in drinking water of blackfoot disease endemic areas: animal experimental model. J. Formosan Med. Assoc. 85, 352-358.
50. Lu, F.J. (1990). Fluorescent humic substances and blackfoot disease in Taiwan. Appl. Organometallic Chem. 4, 191-195.
51. Lu, F.J. (1990). Blackfoot disease: arsenic or humic acid? Lancet 336, 115-116.
52. 陳盈君。(1998)。腐植酸造成睪丸細胞株TM4生長延緩的探討。台大醫學院生化學研究所碩士論文。
53. 陳淑君。腐植酸引發睪丸細胞株TM4產生G1 arrest機制之再探討。台大醫學院生化學研究所碩士論文。
54. Lu, F.J., Lee, T.C., Pang, V.F., Huang, T.S. (1997). Humic acid-induced testicular morphological changes in rats. Bull. Environ. Contam. Toxicol. 58, 619-627.
55. Schnitzers, M.T. (1982). Chemical and microbiological properties. In Page, A.L., eds, Methods of soil analysis, part 2. Academic Press, New York, NY, pp 581-594.
56. Sandell, E.B. (1959). Colorimetric determination of trace metals, Interscience: New York.
57. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951). Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265-275.
58. Tseng, W.P., Chen, W.Y., Sung, J.L., Chen, J.S. (1961). A clinical study of blackfoot disease in Taiwan, an endemic peripheral vascular disease. Mem. Coll. Med. Natl. Taiwan Univ. 7: 1—8
59. Chen, K.P., Wu, H.Y. (1962). Epidemiologic studies on blackfoot: 2. study of source of drinking water in relation to the disease. J. Formosan Med. Assoc. 61, 611-618.
60. Chen, K.P., Wu, H.Y. (1969). Epidemiologic studies on blackfoot in Taiwan, China. 6. Effect of the piped water supply on occurrence and disease progress of blackfoot disease. J. Formosan Med. Assoc. 68, 291-295.
61. Huang, T.S., Lu, F.J., Tsai, C.W., Chopra, I.J. (1994). Effect of humic acids on thyroidal function. J. Endocrinol. Invest. 17: 787—791.
62. Lu, F.J., Liu, T.M. (1986). Fluorescent compounds in drinking water of blackfoot disease endemic areas: animal experimental model. J. Formos. Med. Assoc. 85: 352-358.
63. Huang, T.S., Lu, F.J., Tsai, C.W. (1995). Tissue distribution of absorbed humic acids. Environ. Geochem. Health. 17: 1—4.
64. Lu, F.J., Lu, J.Y. (1987). Serum lipid peroxides in patients with Blackfoot disease. J. Formos. Med. Assoc. 86: 76—80.
65. Peng, A., Wang, W.H., Wang, C.X., Wang, Z.J., Rui, H.F., Wang, W.Z., Yang, Z.W. (1999). The role of humic substances in drinking water in Kashin-Beck disease in The role of humic substances in drinking water in Kashin-Beck disease in China. Environ. Health. Persp. 107: 293-6.
66. Minotti, G. (1993). Sources and role of iron in lipid peroxidation. Chem. Res. Toxicol. 6, 134-146.
67. Braughler, J.M., Duncan, L.A., Chase, R.L. (1986). The involvement of iron in lipid peroxidation. J. Biol. Chem. 261, 10282-10289.
68. Slawinska, D., and Slawinki, J. (1975). Spectroscopic study on mild oxidation of humus acids. II. Influence of light on oxidation with molecular oxygen. Pol. J. Soil. Sci. 8, 49-58.
69. Zepp, R.G., Wolfe, N.L., Baughman, G.L., Hollis, R.C. (1977). Singlet oxygen in natural waters. Nature 267, 421-423.
70. Cooper, W.J., Zika, R.G. (1983). Photochemical formation of hydrogen peroxide in surface and ground waters exposed to sunlight. Science 220, 711-712.
71. Gau, R.J., Yang, H.L., Suen, J.L. and Lu, F.J. (2001). Induction of oxidative stress by humic acid through increasing intracellular iron: a possible mechanism leading to atherothrombotic vascular disorder in blackfoot disease. Biochem. Biophys. Res. Commun. 283: 743-749.
72. Bernacchi, F., Ponzanelli, I., Minunni, M., Falezza, A., Loprieno, N., Barale, R. (1996). In vivo cytogenetic effects of natural humic acid. Mutagenesis 11, 467-9.
73. Liu, Q., Jiao, Q.C., Huang, X.M., Jiang, J.P., Cui, S.Q., Yao, G.H., Jiang, Z.R., Zhao, H.K., Wang, N.Y. (1999). Genotoxicity of drinking water from Chao Lake. Environ. Res. 80, 127-31.
74. Hong, C.L., Lu, F.J., Lu, M.F., Chiang, H.S., Shimizu, H. (1991). Mutagenic screening of the active components of fluorescent humic substances in artesian well water of a black-foot disease endemic area in southwestern Taiwan (abstract). Mutat. Res. 252, 90.
75. Lu, F.J., Chiang, H.S., Lu, M.F., Shimizu, H. (1993). Mutagenicity of drinking well water. Bull. Environ. Contam. Toxicol. 51, 545-550.
76. Stevens, R.G., Jones D.Y., Micozzi M.S., Taylor P.R. (1988). Body iron stores and the risk of cancer. N. Engl. J. Med. 319, 1047-1052.
77. Toyokuni, S. (1996). Iron-induced carcinogenesis: the role of redox regulation. Free Rad. Biol. Med. 20, 553-566.
(2)
1. Sokoloff, L. (1988). Kashin-Beck disease: current status. Nutr. Rev. 46, 113-119.
2. Allander, E. (1994). Kashin-Beck disease. An analysis of research and public health activities based a bibliography 1849-1992. Scand. J. Rheumatol. 23 (Suppl 99), 1-36.
3. Jurenskij, I. M. (1849). Malformation among people living on the banks of the Urov in Eastern Siberia. Tr Imperatorskogo Vol’nogo Ekonomiceskogo Obscestva Saint Petersburg 2, 87-91.
4. Kashin, N. I. (1859). The decription of endemic and other disease, prevailing in the Urov-river area. The records of physico-medical scientific society attached to the Moscow University. Jan 3.
5. Kashin, N. I. (1861). Medical and topographyical description of knjaz’-Konstantin region, Nercinskij okrug. Moskovskaja Medicinskaja Gazata 1-10, 1-82.
6. Kashin. N. I. (1861). Information on the spread of goiter and cretinism on the territory of the Russian Empire. Moskovskaja Medicinskaja Gazata 39-51, 329-479.
7. Kashin, N. I. (1862). Report on the occurrence of goiter and cretinism in the Russian Empire. Dissertation.
8. Kashin, N. I. (1868-9). Goitre and cretinism within and beyond Russia, especially in the Lena valley and other parts of the Irkutsk province. In Protokoly Obscestva Vracej Vostocnoj Sibiri (The records of the Scientific Medical Society of the Eastern Siberia). Irkutsk 1-206.
9. Sokoloff, L. (1989). The history of Kashin-Beck disease. N. Y. State J. Med. 89, 343-351.
10. Sokoloff, L. (1987). In Ain Symposium Proceedings, Nutrition ’87, O. A. Levander, Ed. (New York: Van Nostrand Reinhold), pp. 61-63.
11. Yang, C. L., Bodo, M., Notbohm, H., Peng, A., and Muller, P. K. (1991). Fulvic acid disturbs processing of procollagen II in articular cartilage of embryonic chicken and may also cause Kashin-Beck disease. Eur. J. Biochem. 202, 1141-1146.
12. Peng, A., Yang, C. L., Rui, H. F., and Li, H. (1992). Study on the pathogenic factors of Kashin-Beck disease. J. Toxicol. Environ. Health 35, 79-90.
13. Lin, C. C. (1959). Studies on Kashin-Beck’s disease in Taiwan. J. Japan Pathol. Assoc. 48, 817-828.
14. Mathieu, F., Begaux, F., Lan, Z. Y., Suetens, C., and Hinsenkamp, M. (1997). Clinical manifestations of Kashin-Beck disease in Nyemo Valley, Tibet. Int. Orthop. (SICOT) 21, 151-156.
15. Wang, Y. Z., Yang, Z.Y., Gilula, L. A., and Zhu, C. R. (1996). Kashin-Beck disease: radiography appearance in the hands and wrists. Radiology 201, 265-270.
16. 莫東旭、杜忠民、張增鐵、金軍。(1982)。大骨節病病區和非病區胎兒手指骨軟骨的病理形態學對比觀察。中國地方病學雜誌 第一期 31-33頁。
17. 莫東旭。(1982)。大骨節病軟骨壞死的病理組織學及其臨床意義。中國地方病學雜誌 第一期 116-119頁。
18. Sokoloff, L. (1990). Acquired chondronecrosis. Ann. Rheum. Dis. 49, 262-264.
19. 韓從、李廣元、曹署光、楊建國、衛彥治、任瑛云。(1983)。大骨節病病區兒童血液GSH-Px、TBA、FFA測定結果的分析。中國地方病學雜誌第二期65-68頁。
20. Ge, K., and Yang, G. (1993). The epidemiology of selenium deficiency in the etiological study of endemic disease in China. Am. J. Clin. Nutr. Suppl. 57, 259S-63S.
21. 牛光厚、張保振、李祥禎、劉錦先、朱振源、侯少范。(1984)。硒防治大骨節病兩年X線效果研究及病因學探討。中國地方病學雜誌第三卷第三期197-201頁。
22. Wei, X., Wright, G. C. JR., and Stokoloff, L. (1986). The effect of sodium selenite on chondrocytes in monolayer culture. Arthr. Rheum. 29, 660-664.
23. Hayes, M. H. B. et al. (1989). Humic substances II. A Wiley-Interscience publication press.
24. Aiken, G. R., McKnight, D. M., Wershaw, R.L., and MacCarthy, P. (1985). An introduction to humic substances in soil, sediment, and water. In Humic Substances in Soil, Sedment, and Water, G. R. Aiken, D. M. McKnight, R. L., Wershaw, and P., MacCarthy, Eds. (New York: John Wiley & Sons), pp. 1-9.
25. Hartenstein, R. (1981). Sludge decomposition and stabilization. Science 212, 743-749.
26. Rex, R. W. (1960). Electron paramagnetic resonance studies of stable free radicals in lignins and humic acids. Nature 188, 1185-1186.
27. Atherton, N. M., Cranwell, P. A., Floyd, A. J., Haworth, R. D. (1967). Humic acid. I. ESR spectra of humic acids. Tetrahedron 23, 1653-1667.
28. Schnitzer, M., Skinner, S. I. M. (1969). Free radicals in soil humic compounds. Soil Sci. 108, 383-390.
29. Halliwell, B., and Gutteridge, J. M. C. (1989). Free Rad. Biol. Med. Oxford: Clarendon press:1-20.
30. Machlin, L. J, Bendich, A. (1987) Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1, 441-5.
31. Davies, K. J. A. (1987) Protein damage and degradation by oxygen radicals. J. Biol. Chem. 262, 9895-901.
32. Cacciuttolo, M. A., Trinh, L., Lumpkin, J. A., Rao, G. (1993) Hyperoxia induces DNA damage in mammalian cells. Free Rad. Bio. Med. 14, 267 -76.
33. Shingu, M., Isayama, T., Yasutake, C., et al. (1994) Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation. Inflammation 18, 613-623.
34. Barchowsky, A., Munro, R., Morana, S. J., Vincenti, M. P. and Treadwell, M. (1995). Oxidant-sensitive and phosphorylation-dependent activation of NF-kappa B and AP-1 in endothelial cell. Am. J. Physiol. 269, L829-836.
35. Abate, C., Patel, L., Rauscher, F. J., III, and Curran, T. (1990). Redox regulation of fos and jun DNA-binding activity in vitro. Science 249, 1157-61.
36. Dotto, G., Gilman, M., Maruyama, M., and Weinberg, R. (1986). c-myc and c-fos expression of differentiating in mouse primary keratinocytes. EMBO J. 5, 2853-57.
37. Liang, H. J., Tsai, C. L., and Lu, F. J. (1998). Oxidative stress induced by humic acid solvent extraction fraction in cultured rabbit articular chondrocytes. J. Toxicol. Health (Part A) 54, 477-489.
38. Liang, H. J., Tsai, C. L., Chen, P. Q., and Lu, F. J. (1999). Oxidative injury induced by synthetic humic acid polymer and monomer in cultured rabbit articular chondrocytes. Life Sci. 65, 1163-1173.
39. Huang, T. S., Lu, F. J., Tsai, C. W. (1995). Tissue distribution of absorbed humic acids. Environ. Geochem. Health 17, 1-4.
40. Peng, A. Wang, W. H., Wang, C. X., Wang, Z. J., Rul, H. F., Wang, W. Z., and Yang, Z. W. (1999). The role of humic substances in drinking water in Kashin-Beck disease in China. Environ. Health Perspect. 107, 293-296.
41. Wang, K., Xu, S. J., Zhang, F. H., et al. (1991). Free radicals-induced abnormal chondrocytes, matrix and mineralization. Chinese Med. J. 104, 307-312.
42. Yang, C., Bodo, M., Notbohm, H., et al. (1991). Fulvic acid disturbs processing of procollagen collagen II in articular cartilage of embryonic chicken and may also cause Kashin-Beck disease. J. Biochem. 202, 1141-1146.
43. Yang, C., Niu, C., Bodo, M., et al. (1993). Fulvic acid supplementation and selenium deficiency disturb the structural integrity of mouse skeletal tissue. Biochem. J. 289, 829-835.
44. Anderson, H.C. (1995). Molecular biology of matrix vesicles. Clin. Orthop. Relat. Res. 314, 266-280.
45. Noble, B.S, and Reeve, J. (2000). Osteocyte func tion, osteocyte death and bone fracture resistance. Mol. Cell. Endocrinol. 159, 7-13.
46. Klein-Nulendt, J., Van der Plas, A., Semeins, C.M., Ajubi, N.E., Frangos, J.A.,
Nijweide, P.J., and Burger, E.H. (1995). Sensitivity of osteocytes to biomechanical stress in vivo. FASEB J. 9, 441-445.
47. Mundy, G.R. (1995). Osteoblasts, bone formation and mineralization. In: Fogelman I, editor.Bone remodeling and its disorders. London: Maetin Dunitz; p. 27-38.
48. Gehron, R.P. (1996). Vertebrate mineralized matrix proteins: Structure and function. Connect. Tiss. Res. 35, 131-136.
49. Heinegard, D., and Oldberg, A. (1989). Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J. 3, 2042-2051.
50. Donley, G.E., and Fitzpatrick, L.A. (1998). Noncollagenous matrix proteins controlling mineralization: Possible role in pathologic calcification of vascular tissue. Trends Cardiovasc. Med. 8, 199-206.
51. Weiss, R.E., and Reddi, A.H. (1981) Role of fibronectin in collagenous matrixinduced mesenchymal cell proliferation and differentiation in vivo. Exp. Cell Res. 133, 247-254.
52. Oldberg, A., Franzen, A., and Heinegard, D. (1988). The primary structure of a cell-binding bone sialoprotein. J. Biol. Chem. 263, 19340-19342.
53. Stein, G.S., and Lian, J.B. (1993). Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocrine Rev. 14, 424-442.
54. Lowry, O.H. (1995). Micromethods for the assay of enzyme II specific procedures: Alkaline phosphatase. Method. Enzymol. 4, 371-372.
55. Grynkiewicz, G., Poenie, M. & Tsien, R. Y. (1985). A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biochem. 260, 3440-3450.
56. Vuillaume, M., (1987). Reduced oxygen species, mutation, induction and cancer initiation. Mutation Res. 186, 43-72.
57. Dettmer, C. M., Kramer, S., Gottlieb, S. F., Aponte, G. E., (1968). Carcinogenic properties of increased oxygen tensions. I. Effects on radiation-induced mammary tumors. J. Natl. Cancer Inst. 41, 751-756.
58. Bruyninckx, W. J., Mason, H. S., Morse, S. A., (1978). Are physiological oxygen concentrations mutagenic? Nature 274, 606-607.
59 Sturrock, J.E., Nunn, J.F., (1978). Chromosomal damage and mutations after exposure of Chinese hamster cells to high concentrations of oxygen. Mutation Res. 57, 27-33.
60. Moody, C. S., Hassan, H. M., (1982). Mutagenicity of oxygen free radicals. Proc. Natl. Acad. Sci. USA 79, 2855-2859.
61. Leprat, P., Ratinaud, M. H. Maftah, A., Petit, J. M., and Julien, R., (1990). Use of nonyl acridine orange and Rhodamine 123 to follow biosynthesis and functional assembly of mitochondrial membrane during L1210 cell cycle. Experimental Cell Res. 186, 130-137.
62. Sweet, S., and Singh, G., (1999). Changes in mitochondrial mass, membrane potential, and cellular adenosine triphosphate content during the cell cycle of human leukemic (HL-60) cells. J. cellular physiol. 180, 91-6.
(3)
1. Watanabe, K., Watanabe, H.Y., Goto, Y., Yamamoto, N. and Yoshizaki, M. (1975). Studies on the active principles of magnolia bark. Centrally acting muscle relaxant activity of magnolol and honokiol. Japan J. Pharmacol. 25, 605-607.
2. Watanabe, K, Watanabe, H., Goto, Y., Yamaguchi, M., Yamamoto, N., Hagino, K. (1983). Pharmacological properties of magnolol and honokiol extracted from Magnolia officinalis: central depressant effects. Planta Med. 49, 103-108.
3. Ho, K.Y., Tsai, C.C., Chen, C.P., Huang, J.S., Lin, C.C. (2001). Antimicrobial activity of honokiol and magnolol isolated from Magnolia officinalis. Phytother. Res. 15, 139-141.
4. Clark, A.M., Elferaly, F.S. and Li, W.S. (1981). Antimicrobial activity of phenolic constituent of Magnolia grandiflora L. J. Pharm. Sci. 70, 951-952.
5. Hattori, M., Endo, Y., Takebe, S., Kobashi, K., Fukasaku, N., and Namba, T. (1984). Metabolism of magnolol from Magnoliae cortex.1. Application of liquid of chromatography-mass spectrometry to the analysis of metabolities of magnolol in rats. Biochem. Pharm. 32, 5010-5017.
6. Teng, C.M., Chen, C.C., Ko, F.N., Lee, L.G., Huang, T.F., Chen, Y.P. and Hsu, H.Y. (1988). Two antiplatelet agents from Magnolia officinals. Thromb. Res. 50, 757-765.
7. Teng, C.M., Yu, S.M., Chen, C.C., Huang, Y.L., and Huang, T.F. (1990) EDRF-release and Ca2+-channel blockade by magnolol, and antiplatelet agent isolated from Chinese herb Magnolia officinalis, in rat thoracic aorta. Life Sci. 47, 1153-1161.
8. Hirano, T., Wakasugi, A., Oohara, M., Oka, K. and Sashida, Y. (1991). Suppression of mitogen-induced proliferation of human peripheral blood lymphocytes by plant lignans. Plant Med. 57, 331-334.
9. Wang, J.P., Hsu, M.F., Raung, S.L., Chen, C.C., Kuo, J.S. and Teng, C.M. (1992). Anti-inflammatory and analgesic effects of magnolol. Naunyn-Schmiedebergs Arch. Pharmaco. 346, 707-712.
10. Wang, J.P., Raung, S.L., Chen, C.C., Kuo, J.S. and Teng, C.M. (1993). The inhibitory effect of magnolol on cutaneous permeability in mice is probably mediated by a nonselective vascular hyporeactivity to mediators. Naunyn-Schmiedebergs Arch. Pharmaco. 348, 663-669.
11. Lo, Y.C., Teng, C.M., Chen, C.F., Chen, C.C. and Hong, CY. (1994). Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation. Biochem. Pharm. 47, 549-553.
12. Lin, M.H., Chao, H.T., and Hong CY. (1995). Magnolol protects human sperm motility against lipid peroxidation: a sperm head fixation method. Arch. Androlo. 34, 151-156.
13. Tsai, T.H., Lee, T.F., Chen, C.F. and Wang, L.C. (1995). Modulatory effects of magnolol on potassium-stimulated 5-hydroxytryptamine release from rat cortical and hippocampal slices. Neuroscience Letters 186, 49-52.
14. Tsai, T.H.,Tsai, W.J., Chou, C.J. and Chen, C.F. (1995). Inhibition by honokiol of collagen-induced platelet 5-HT release. Pharm. Sci. 1, 239-241.
15. Taira, J., Ikemoto, T., Mimura, K., Hagi, A., Murakami, A., Makino, K. (1993). Effective inhibition of hydroxyl radicals by hydroxylated biphenyl compounds. Free Rad. Res. Commun. 19, S71-7.
16. Ellis, R., Yuan, J., and Horvitz, H.R. (1991). Mechanism and function of cell death. Annu. Rev. Cell Biol. 7, 663-698.
17. Maximilian, L., Marcha, L., and Edwin, H. (1993). Apoptosis and necrosis: basic types and mechanisms of cell death. Arch. Pathol. Lab. Med. 117, 1208-1214.
18. Gerschenson, L.E. (1992). Apoptosis: a different type of cell death. FASEB J. 6, 2450-2455.
19.Zhang, Y.H., Takahashi, K., Jiang, G.Z., Kawai, M., Fukada, M., and Yokochi, T. (1993). In vivo induction of apoptosis (programmed cell death) in mouse thymus by administration of lipopolysaccharide. Infect. Immun. 61, 5044-5048.
20. Kerr, J.F., Wyllie, A.H., Currie, A.R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Brit. J. Cancer 26, 239-257.
21. Raff, M.C. (1992). Social controls on cell survival and cell death. Nature 356, 397-400.
22. Mignotte, B. and Vayssiere, J.L. (1998). Mitochondria and apoptosis. Eur. J. Biochem. 252, 1-15.
23. Martin, S.J. and Green, D.R. (1995). Apoptosis and cancer: the failure of controls on cell death and cell survival. Crit. Rev. Oncol. Hematol. 16, 137-153.
24. Brown, D.G., Klrinr, L., and Tenniswood, M. (1990). The biochemistry of cell death by apoptosis. Biochem. Cell Biol. 88, 1071-1074.
25. Earnshaw, W.C., Martins, L.M., Kaufmann, S.H. (1999). Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Ann. Rev. Biochem. 68, 383-424, 1999.
26. Nunez, G., Benedict, M.A., Hu, Y. and Inohara, N. (1998). Caspases: the proteases of the apoptotic pathway. Oncogene 17, 3237-3245.
27. Nagata, S. (1997). Apoptosis by death factor. Cell 88, 355-365.
28. Stennicke, H.R., Salvesen, G.S. (2000). Caspases- controlling intracellular signals by protease zymogen activation. Biochem. Biophys. Acta 1477, 299-306.
29. Earnshaw, W.C., Martins, L.M., Kaufmann, S.H. (1999). Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Ann. Rev. Biochem. 68, 383-424.
30. Green, D.R., Reed, J. C., (1998). Mitochondria and apoptosis. Science 281, 1309-1321.
31. Halestrap, A.P., Doran, E., Gillespie, J.P., O’Toole, A. (2000). Mitochondria and cell death. Biochem. Soc. T. 28, 170-177.
32. Desagher, S., Martinou, J.C. (2000). Mitochondria as the central control point of apoptosis. Trends cell Biol. 10, 369-377.
33. Newmeyer, D.D., Farschon, D.M., Reed, J.C., (1994). Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria. Cell 79, 353-364.
34. Kroemer, G., (1997). The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nature Med. 3, 614-620.
35. Liu, X., Kim, C.N., Yang, J., Jemmerson, R., Wang, X., (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157.
36. Kluck, R.M., Bossy-Wetzel, E., Green, D.R., Newmeyer, D.D., (1997). The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132-1136.
37. Kluck, R.M., Martin, S.J., Hoffman, B.M., Zhou, J.S., Green, D.R., Newmeyer, D.D., (1997). Cytochrome c activation of CPP32-like proteolysis plays a critical role in a Xenopus cell-free apoptosis system. EMBO J. 16, 4639-4649.
38. Yang, J., Liu, X., Bhalla, K., Kim, C.N., Ibrado, A.M., Cai, J., Peng, T.I., Jones, D.P., Wang, X., (1997). Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129-1132.
39. Cai, J., Yang, J., Jones, D.P., (1998). Mitochondrial control of apoptosis: the role of cytochrome c. Biochim. Biophys. Acta 1366, 139-149.
40. Zou, H., Henzel, W.J., Liu, X., Lutschg, A., Wang, X., (1997). Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90, 405-413.
41. Li, P., Nijihawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S., and Wang, X., (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.
42. Clement, M.V., Hirpara, J.L., Chawdhury, S.H., Pervaiz, S. (1998). Chemopreventive agent resveratrol, a natural product derived from grapes, trigger CD95 signaling-dependent apoptosis in human tumor cells. Bood 92, 999-1002.
43. Wei, Y.Q., Zhao, X., Kariya, Y., Fukata, H., Teshigawara, K., Uchida, A. (1994). Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res. 54, 4952-4957.
44. Inoue, M., Suzuki, R., Koide, T., Sakaguchi, N., Ogihara, Y., Yabu, Y. (1994). Antioxidant, gallic acid, induces apoptosis in HL-60 cells. Biochem. Biophys. Res. Commun. 204, 898-904.
45. Zhao, Y., Cao, J., Ma, H., Liu, J. (1997). Apoptosis induced by tea polyphenols in HL-60 cells. Cancer Lett. 121, 163-167.
46. Chu, C.Y., Tsai, Y.Y., Wang, C.J., Lin, W.L., Tseng, T.H. (2001). Induction of apoptosis by esculetin in human leukemia cells. Eur. J. Pharmacol. 416, 25-32.
47. Bedner, E., Li, X., Gorczyca, W., Melamed, M.R., Darzynkiewicz, Z. (1999). Analysis of apoptosis by laser scanning cytometry. Cytometry 35, 181-195.
48. Vander Heiden, M.G., Chandel, N.S., Williamson, E.K., Schumacker, P.T., Thompson, C.B. (1997). Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 91, 627-637.
49. Leprat, P., Ratinaud, M. H. Maftah, A., Petit, J. M., and Julien, R., (1990). Use of nonyl acridine orange and Rhodamine 123 to follow biosynthesis and functional assembly of mitochondrial membrane during L1210 cell cycle. Experimental Cell Res. 186, 130-7.
50. Sweet, S., and Singh, G., (1999). Changes in mitochondrial mass, membrane potential, and cellular adenosine triphosphate content during the cell cycle of human leukemic (HL-60) cells. J. Cellular Physiol. 180, 91-6.
51. Ronot, X., Benel, L., Adolphe, M., and Mounolou, J.C., (1986). Mitochondrial analysis in living cells:the use of rhodamine 123 and flow cytometry. Biol. cell 57, 1-8.
52. Lansiaux, A., Facompre, M., Wattez, N., Hildebrand, M.P., Bal, C., Demarquay, D., et al. (2001). Apoptosis induced by the homocamptothecin anticancer drug BN80915 in HL-60 cells. Mol. Pharmacol. 60, 450-461.
53. Darzynkiewicz, Z., Juan, G., Li, X., Gorczyca, W., Murakami, T., Traganos, F. (1997). Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis). Cytometry 27, 1-20.
54. Farber, A., Kitzmiller, T., Morganelli, R.M., Pfeiffer, J., Groveman, D., Wagner, R.J., et al. (1999). A caspase inhibitor decreases oxidized low-density lipoprotein-induced apoptosis in bovine endothelial cells. J. Surg. Res. 85, 323-330.
55. Fadok, V.A., Voelker, D.R., Campbell, P.A., Cohen, J.J., Bratton, D.L., Henson, P.M. (1992). Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148, 2207—2216.
56. van Heerde, W.L., Robert-Offerman, S., Dumont, E., Hofstra, L., Doevendans, P.A., Smits, J.F., et al. (2000). Markers of apoptosis in cardiovascular tissues: focus on Annexin V. Cardiovasc. Res. 45, 549-559.
57. Porn-Ares, M.I., Ares, M.P.S., Orrenius, S. (1998). Calcium signaling and the regulation of apoptosis. Toxicol. in Vitro 12, 539-543.
58. Kaufman, SN. (1989) Induction by endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin and other cytotoxic anticancer drugs: a cautionary note. Cancer Res. 49, 5870-5878.
59. Calabresse, C, Barbey, S, Venturini, L, Balitrand, N, Degos, L, Fenaux, P, Chomienne, C. (1995) In vitro treatment with retinoids or the topoisomerase inhibitor, VP-16, evidences different functional apoptotic pathways in acute promyelocytic leukemic cells. Leukemia 9, 2049-2057.
60. Friesen, C, Fulda, S, Debatin, KM. (1999) Cytotoxic drugs and the CD95 pathway. Leukemia 13, 1854-1858.
61. Beltz, L, Moran, R, Elsawy, O, Sadler, J, Jurgenson, J. (1999) The effects of telomerase inhibitors on lymphocyte function. Anticancer Res. 19, 3205-3211.
62. Wilmore, DW, Schloerb, PR, Ziegler, TR. (1999) Glutamine in the support of patients following bone marrow transplantation. Curr. Opin. Clin. Nutr. Metab. Care 2, 323-327.
63. Li, H, Zhu, H, Xu, CJ, Yuan, J. (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501.
64. Kluck, RM, Esposti, MD, Perkins, G, Renken, C, Kuwana, T, Bossy-Wetzel, E, et al. (1999) The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilizationof the mitochondrial outer membrane that is enhanced by cytosol. J. Cell Biol. 147, 809-822.
65. Yang, J, Liu, X, Bhalla, K, Kim, CN, Ibrado, AM, Cai, J, et al. (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129-1132.
66. Kluck, RM, Bossy-Wetzel, E, Green, DR, Newmeyer, DD. (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132-1136.
67. Stridh, H, Kimland, M, Jones, DP, Orrenius, S, Hampton, MB. (1998) Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis. FEBS Lett. 429, 351-355.
68. Gottlieb, RA, Nordberg, J, Skowronski, E, Babior, BM. (1996) Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification. Proc. Natl. Acad. Sci. USA 93, 654-658.
69. Thangaraju, M, Sharma, K, Leber, B, Andrews, DW, Shen, SH, Srikant, CB. (1999) Regulation of acidification and apoptosis by SHP-1 and Bcl-2. J. Biol. Chem. 274, 29549-29557.
70. Goossens, JF, Henichart, JP, Dassonneville, L, Facompre, M, Bailly, C. (2000) Relation between intracellular acidification and camptothecin-induced apoptosis in leukemia cells. Eur. J. Pharm. Sci. 10, 125-131.
71. Matsuyama, S, Llopis, J, Deveraux, QL, Tsien, RY, Reed, JC. (2000) Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis. Nat. Cell Biol. 2, 318-325.
72. Harman, AW, Maxwell, MJ. (1995) An evaluation of the role of calcium in cell injury. Annu. Rev. Pharmcol. Toxicol. 35, 129-144.
73. Distelhorst, CW, Dubyak, G. (1998) Role of calcium in glucocorticosteroid-induced apoptosis of thymocytes and lymphoma cells: resurrection of old theories by new findings. Blood 91, 731-734.
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