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研究生:林慧茹
研究生(外文):Hui-Ju Lin
論文名稱:青光眼的分子遺傳學及治療學研究
論文名稱(外文):Molecular Genetic and Therapeutic Study of Glaucoma
指導教授:范聖興蔡輔仁蔡輔仁引用關係
指導教授(外文):Seng-Sheen FanFuu-Jen Tsai
學位類別:博士
校院名稱:東海大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:英文
論文頁數:131
中文關鍵詞:青光眼基因多型性NMDA蘆薈大黃素銅鋅超氧化物岐化脢
外文關鍵詞:glaucomaE-cadheringenetic polymorphismNMDAaloe-emodinCu-Zn SOD
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青光眼是一種會嚴重危害視力的眼疾,甚至在開發地區青光眼仍是造成失明的第二位,因為沒有有效的預測因子,許多人在視野已經縮小了,才警覺到罹患青光眼。近年來研究開發許多先進的藥物用以控制眼壓。然而,仍有許多青光眼病人最後仍然失明。本研究,我們先以基因多型性來尋找台灣人青光眼的基因標的,我們發現許多對青光眼有意義的基因多型性。 其中之ㄧ是E-cadherin基因的3’UTR C/T基因多型性,在開放性青光眼與正常人的差異有顯著的意義。 3’UTR C/T基因多型性中”C”基因型在開放性青光眼的病人中有明顯的增加。此外,我們以NMDA加到N18視神經細胞,來製造青光眼的體外模式,再以此模式在我們發現蘆薈大黃素的代謝物,能有效的經由內凋零路徑將神經細胞凋零現象減少,我們也發現蘆薈大黃素的代謝產物比它的原始型態更有療效。藉由西方點墨法及螢光報導基因。我們也以蛋白質體學的方式來研究參與此反應的蛋白質,從中發現了Cu-Zn SOD對N18視網膜神經細胞在受到NMDA作用時有保護作用。本研究發現了許多有效的基因標的,用以預知青光眼罹患的可能﹔並發現在青光眼的體外模式中,蘆薈大黃素可以減少N18視網膜神經細胞的凋零現象。
Glaucoma is a vision-threaten disease and it is the second leading cause of blindness even in a developed area. Since there was no useful predicting methods, some patients appreciate the disease till visual field is constricted. There are many advanced drugs produced recently for controlling intraocular pressure. Nevertheless, there are still some glaucoma patients inevitably loss their vision. In this study, we used single nucleotide polymorphisms (SNPs) tried to find useful genetic markers for glaucoma in Taiwan. We had found many meaning SNPs for glaucoma. One of the SNPs which had significant differences was E-cadherin-1 gene 3’-UTR C/T polymorphism. We had found that the incidence of “C” allele of E-cadherin-1 gene 3’-UTR C/T polymorphism was higher in primary open angle glaucoma (POAG) patients. We also established an in vitro model of glaucoma by adding NMDA to N18 retina ganglion cells (RGCs). We found that aloe-emodin metabolites was useful in decreasing apoptosis of NMDA-treated N18 RGCs. Aloe-emodin metabolites decreased apoptosis of NMDA-treated N18 RGCs and it was through intrinsic apoptosis pathway. We also found that the aloe-emodin metabolites was more useful then its parents’ form. Moreover, by proteomics study, we detected that Cu-Zn SOD was important in protecting N18 RGCs from NMDA-induced apoptosis. In our study, we excavated useful markers for predicting POAG in Taiwanese and discovered aloe-emodin metabolites was effective in protecting N18 RGCs in an in vitro model of glaucoma.
Contents
Acknowledgement 3
Abstract in English 4
Abstract in Chinese 5
Introduction 6
Ι. Genetic polymorphisms of glaucoma 6
Ⅱ. Establishing in vitro glaucoma model 12
Ⅲ. Polyphenols were good candidates to decrease apoptosis of
NMDA-treated RGCs 16
Ⅳ.The apoptosis pathway of NMDA-treated RGCs 18
Materials and Methods 20
Ι. Genetic polymorphisms of glaucoma 20
Ⅱ. Establishing in vitro glaucoma model 23
Ⅲ. Preparation of polyphenols metaboloites 28
Ⅳ. Detecting the molecules involved in the apoptosis pathway 30
Ⅴ.Determining the proteins involved in the polyphenols
metabolites and NMDA-treated RGCs by LC-MS-MS 31
Ⅵ.In vivo studies of the effects of polyphenol metabolites on
NMDA-induced apoptosis of retina ganglion cells 35
Ⅶ. Statistical analysis 36

Results 37
Ι. Genetic polymorphisms of glaucoma 37
Ⅱ. In vitro model of glaucoma 39
Ⅲ. The effects of polyphenols metabolites on NMDA-induced
apoptosis of N18 RGCs 40
Ⅳ. Detecting the apoptosis pathway of aloe-emodin metabolites and
NMDA-treated N18 RGCs 42
Ⅴ.Aloe-emodin metabolites was also effective in decreasing
NMDA-induced apoptosis on N18 RGCs in vivo 44
Ⅵ. Aloe-emodin metabolites decreased NMDA-induced apoptosis of RGCs
by increasing of Cu-Zn superoxide dismutase 44

Discussion 49
Ι. Genetic polymorphisms of glaucoma 49
Ⅱ. Aloe-emodin metabolites was effective in decreasing apoptosis of
NMDA-induced N18 RGCs 53
Ⅲ.Aloe-emodin metabolites regulated NMDA-treated N18 RGCs
by intrinsic apoptosis pathway 54
Ⅳ. Aloe-emodin was effective in decreasing apoptosis of N18 RGCs in vivo 54
Ⅴ. Aloe-emodin metabolites decreased apoptosis of NMDA-treated
RGCs by Cu-Zn SOD 55
Conclusion 60
References 61
Figures and legends 80
Tables 112
Curriculum vitae 128
References
1. Quiqley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996;80:389-403.
2.Shields MB, Ritch R, Krupin T. Classification of the glaucomes. In: The glaucoma. St Louis: Mosby-Year Book In, 1996;2:717-725.
3.Wolfs RC, Borger PH, Ramrattan RS, Klaver CC, Hulsman CA, Hofman A, Vingerling JR, Hitchings RA, de Jong PT. Changing views on open-angle glaucoma: definitions and prevalences—The Rotterdam Study. Invest Ophthalmol Vis Sci 2000;41:3309-3321.
4. Garcia Valenzuela E, Gorczycaw, Darzynkiewicz Z, Sharna SC. Apoptosis in adult retinal ganglion cells after axotomy. J Neurobiol 1994;25:431-438.
5. Garcia-Valenzuela E, Shareef S, Walsh J, Sharma SC. Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp Eye Res 1995;61:33-44.
6. Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt J, Singh K. Relationship between intraocular pressure and primary open angle glaucoma among white and black Amenicans. The Baltimore Eye Survey Arch Ophthalmol 1991;109:1090-1095.
7. Kirwan RP, Crean JK, Fenerty CH, Clark AF, O'Brien CJ. Effect of cyclical mechanical stretch and exogenous transforming growth factor-beta1 on matrix metalloproteinase-2 activity in lamina cribrosa cells from the human optic nerve head. J Glaucoma 2004;13:327-334.
8. Fingert JH, Heon E, Liebmann JM, Yamamoto T, Craig JE, Rait J, Kawase K, Hoh ST, Buys YM, Dickinson J, Hockey RR, Williams-Lyn D, Trope G, Kitazawa Y, Ritch R, Mackey DA, Alward WL, Sheffield VC, Stone EM. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum Mol Genet 1999;8:899-905.
8.Klemetti A. Low-tension glaucoma--a disease for ophthalmology or internal medicine? Duodecim 1997;113:1425-1426.
9.Stuart JM, Glaucoma, apoptosis, and neuroprotection. Current Opinion in Ophthalmology 1997;8:28-37.
10.Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR, Sunden SL, Nishimura D, Clark AF, Nystuen A, Nichols BE, Mackey DA, Ritch R, Kalenak JW, Craven ER, Sheffield VC. Identification of a gene that causes primary open angle glaucoma. Science 1997;31:275:668-670.
11.Ortego J, Escribano J, Coca-Prados M. Cloning and charaterization of substracted cDNAs from a human ciliary body library encoding TIGR a protein involved in juvenite open angle glaucoma with homologus toneyosin and olfactomodin. FEBs Lett 1997;413:349-353.
12.Kubota R, Noda S, Wang Y, Minoshima S, Asakawa S, Kudoh J, Mashima Y, Oguchi Y, Shimizu N. A novel myosin-like protein (myocilin) expressed in the connecting cilium of photoreceptor molecular cloning, tissue expression, and chromosomal mapping. Genomico 1997;41:360-370.
14. Lin HJ, Tsai CH, Tsai FJ, Chen WC, Chen HY, Fan SS. Transporter associated with antigen processing gene 1 codon 333 and codon 637 polymorphisms are associated with primary open angle glaucoma. Mol Diagn 2004;8:245-252.
15. Lin HJ, Tsai SC, Tsai FJ, Chen WC, Tsai JJ, Hsu CD. Association of interleukin 1 beta and receptor antagonist gene polymorphism with primary open angle glaucoma. Ophthalomiga 2003;217:358-364.
16. Lin HJ, Tsai FJ, Chen WC, Chi YR, Hsu Y, Tsai SW. Association of tumor necrosis factor alpha-308 gene polymorphism with primary open angle glaucoma in Chinese. Eye 2003;17:31-34.
17. Lin HJ, Chen WC, Tsai FJ, Tsai SW. Distribution of p53 codon 72 gene polymorphism with primary open angle glaucoma. Br J Ophthalmol 2002;86:771-773.
18. Drance SM, Schulzer M, Thomas B, Douglas GR. Multivariate analysis in glaucoma use of discriminant analysis in predicating glaucomatous visual field damage. Arch Ophthalmol 1981;6:1019-1022.
19. Laske MC, Connell AMS, Wu S, et al. Risk factor of open-angle glaucoma. Arch Ophthalmol 1995;113:918-924.
20. Tsai FJ, Lin HJ, Chen WC, Tsai CH, Tsai SW. A codon 31ser-arg polymorphism of the WAF-1/CIP-1/p21/tumour suppressor gene in Chinese primary open-angle glaucoma. Acta Ophthalmol Scand 2004;82:76-80.
21. Tsai FJ, Lin HJ, Chen WC, Chen HY, Fan SS. Insulin-like growth factor-II gene polymorphism is associated with primary open angle glaucoma. J Clin Lab Anal 2003;17:259-263.
22. Camras CB, Alm A, Watson P, Stjernschantz J. Latanoprost, a prostaglandin analog, for glaucoma therapy. Efficacy and safety after 1 year of treatment in 198 patients. Latanoprost Study Groups. Ophthalmology 1996;103:1916-24.
23. Kuniyasu H, Ellis LM, Evans DB, Abbruzzese JL, Fenoglio CJ, Bucana CD, Cleary KR, Tahara E, Fidler IJ. Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma. Clin Cancer Res 1999;5:25-33.
24. Nawrocki-Raby B, Gilles C, Polette M, Martinella-Catusse C, Bonnet N, Puchelle E, Foidart JM, Van Roy F, Birembaut P. E-Cadherin mediates MMP down-regulation in highly invasive bronchial tumor cells. Am J Path 2003;163:653-661.
25. Streuli CH, Bailey N, Bissell MJ. Control of mammary epithelial differentiation: basrment membrane induces tissue-specific gene expression on the absence of cell-cell interaction and morphological polarity. J Cell Biol 1991;115:1383-1395.
26. Yap AS. The morphogenetic role of cadherin cell adhesion molecules in human cancer: a thematic review. Cancer Invest 1998;16:252-261.
27. Steinhusen U, Weiske J, Badock V, Tauber R, Bommert K, Huber O. Cleavage and shedding of e-cadherin after induction of apoptosis. J Biol Chem 2001;276:4972-4980.
28. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991;251:1451-1455.
29. Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell 1996;84:345-357.
30. Shapiro L, Fannon AM, Kwong PD, Thompson A, Lehmann MS, Grubel G, Legrand JF, Als-Nielsen J, Colman DR, Hendrickson WA. Structural basis of cell-cell adhesion by cadherins. Nature 1995;374:327-337.
31. Huber O, Bierkamp C, Kemler R. Cadherins and catenins in development. Curr Opin Cell Biol 1996;8:685-691.
32. Vleminckx K, Kemler R. Cadherins and tissue formation: intergrating adhesion and signaling. Bioessays 1999;21:211-220.
33. Yap AS. The morphogenetic role of cadherin cell adhesion molecules in human cancer: a thematic review. Cancer Invest 1998;16:252-261.
34. La Rosa, Francis A, Lee David A. Collagen degradation in glaucoma: will it gain a therapeutic value? Curr opin in ophthalmol. 2000;11:90-93
35. Ando H, Twining SS, Yue BY, Zhou X, Fini ME, Kaiya T, Higginbotham EJ, Sugar J. MMPs and proteinase inhibtors in the human aqueous humor. Invest ophthalmol Vis Sci 1993;343541-343548.
36. Samples JR, Alexander JP, Acott TS. Regulation of the levels of human trabecular matrix metalloproteinases and inhibitor by interleukin-1 and dexamethasone Invest Ophthalmol Vis Sci 1993;34:3386-3395.
37. Yan X, Tezel G, Wax MB, Edward DP. Matrix metalloproteinases and tumor necrosis factor  in glaucomatous optic nerve head. Arch Ophthalnol 2000;118:666-673.
38. Moll R, Mitze M, Frixen UH, Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 1993;143:1731-1742.
39. Berx G, Cleton-Jansen A-M, Nollet F, de Leeuw WJ, van de Vijver M, Cornelisse C, van Roy F. E-cadherin is a tumor/invasion suppressor gene mutated in human lobular breast cancer. EMBO J 1995;14:6107-6115.
40. Bscker KF, Reich U, Schott C, Hufler H. Single nucleotide polymorphisms in the human E-cadherin gene. Hum Genet 1995;96:739-740.
41. Alm A. Ocular circulation. In Adler’s Physiology of the Eye, Hart, W.M., ed. Mosby St. Louis: MO, U.S.A. 1992:198-227.
42.Dawson, T.M. and Snyder, S.H. Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J Neurosci 1994;14:5147-5159.
43.Hardy P, Nuyt AM, Abran D, St-Louis J, Varma DR, Chemtob S. Nitric oxide in retinal and choroidal blood flow autoregulation in newborn pigs: interactions with prostaglandins. Pediat Res 1996;39:487-493.
44.Koss MC. Functional role of nitric oxide in regulation of ocular blood flow. Eur J Pharmacol 1999;374:161-174.
45.Schmetterer L, Krejcy K, Kastner J, Wolzt M, Gouya G, Findl O, Lexer F., Breiteneder H, Fercher AF, Eichler HG. The effect of systemic nitric oxidesynthase inhibition on ocular fundus pulsations in man. Exp Eye Res 1997;64:305-312.
46.Hangai M, Miyamoto K, Hiroi K, Tuijikawa A, Ogura Y, Honda Y, Yoshimura N. Roles of constitutive nitric oxide synthase in postischemic rat retina. Invest Ophthalmol Vis Sci 1999;40:450-458.
47.Lam TT, Tso MO. Nitric oxide synthase (NOS) inhibitors ameliorate retinal damage induced by ischemia in rats. Res Commun Mol Pathol Pharmacol 1996;92:329-340.
48.Neufeld AH, Hernandez MR, Gonzalez M. Nitric oxide synthase in the human glaucomatous optic nerve head. Arc. Ophthalmol 1997;115:497-503.
49.Neufeld AH, Sawada A, Becker B. Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc Nat Acad Sci U.S.A. 1996;96:9944-9948.
50.Dimmeler S, Zeiher AM. Nitric oxide and apoptosis: another paradigm for the double-edged role of nitric oxide. Nitric Oxide 1997;1:275-281.
51.Vorwerk, CK, Hyman BT, Miller JW, Husain D, Zurakowski D, Huang PL, Fishman MC, Dreyer EB. The role of neuronal and endothelial nitric oxide synthase in retinal excitotoxicity. Invest Ophthalmol Vis Sci 1997;38:2038-2044.
52.Siu AW, Reiter RJ, To CH. The efficacy of vitamin E and melatonin as antioxidants against lipid peroxidation in rat retinal homogenates. J Pineal Res 1998;24:239-244.
53.Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Nat Acad Sci U.S.A. 1990;87:1620-1624.
54.Harman D. Free radical theory of aging. Muta. Re. 1992; 275:257-266.
55.Siu A., Reiter RJ, To CH. Pineal indoleamines and vitamin E reduce nitric oxide-induced lippid peroxidation in rat retinal homogenates. J Pineal Res 1997;27:122-128.
56.Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, Motoyama T, Saito Y, Ogawa Y, Miyamoto Y, Nakao K. T-786 → C Mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 1999;99:2864-2870.
57.Farrell AJ, Blake DR, Palmer RMJ, Moncada S. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 1992;51:1219-1222.
58.Klebanoff S. Reactive nitrogen intermediates and antimicrobial activity: role of nitrite. Free Radic Bio Med 1993;14:351-360.
59.Eiserich JP, Cross CE, Jones AD, Halliwell B, van der Vliet A. Formation of nitrating and chlorinating species by reaction of nitrite with hypochlorous acid. J Biol Chem 1996;271:19199-19208.
60.Eiserich JP, Hristova M, Cross CE, Jines AD, Freeman BA, Halliwell B, van der Vliet A. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 1998;391:393-397.
61.van der Vliet A, Eiserich JP, Halliwell B, Cross CE. Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite. J Biol Chem 1997;272:7617-7625.
62.Miyamoto Y, Saito Y, Kajiyama N, Yoshimura M, Shimasaki Y, Nakayama M, Kamitani S, Harada M, Ishikawa M, Kuwahara K, Ogawa E, Hamanaka I, Takahashi N, Kaneshige T, Teraoka H, Akamizu T, Azuma N, Yoshimasa Y, Yoshimasa T, Itoh H, Masuda I, Yasue H, Nakao K. Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension 1998;32:3-8.
63.Pecoits-Filho R, Stenvinkel P, Marchlewska A, Heimburger O, Barant P, Hoff CM. A functional variant of the myeloperoxidase gene is associated with cardiovascular disease in end-stage renal disease patients. Kidney Internat 2003;supplement:S172-176.
64. Kirwan RP, Crean JK, Fenerty CH, Clark AF, O'Brien CJ. Effect of cyclical mechanical stretch and exogenous transforming growth factor-beta1 on matrix metalloproteinase-2 activity in lamina cribrosa cells from the human optic nerve head. J Glaucoma 2004;13:327-334.
65. Golubnitschaja O, Wunderlich K, Decker C, Monkemann H, Schild HH, Flammer J. Molecular imaging of perfusion disturbances in glaucoma. Amino Acids 2002;23:293-299.
66. Wehrwein E, Thompson SA, Coulibaly SF, Linn DM, Linn CL. Acetylcholine protection of adult pig retinal ganglion cells from glutamate-induced excitotoxicity. Invest Ophthalmol Vis Sci 2004;45:1531-1543.
67. Koss MC. Functional role of nitric oxide in regulation of ocular blood flow. Eur J Pharmacol 1999;374: 161-174.
68. Romano C, Li Z, Arendt A, Hargrave PA, Wax MB. Epitope mapping of anti-rhodopsin antibodies from patients with normal pressure glaucoma. Invest Ophthalmol Vis Sci 1999;40:1275-1280.
69. Tezel G. Hernandez R. Wax MB. Immunostaining of heat shock proteins in the retina and optic nerve head of normal and glaucomatous eyes. Arch Ophthalmol 2000;118:511-518.
70. Lipton SA, Rosenberg RA. Mechanisms of disease: Excitatory amino acids as a final common pathway in neurologic disorders. N Engl J Med 1994;330:613–622.
71. Lucas DR, Newhouse JP. The toxic effect of sodium l-glutamate on the inner layers of the retina. Am Med Assoc Arch Ophthalmol 1957;58:193–201.
72. Olney JW, Ho OL: Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine. Nature 1970;227:609–611.
73. Olney JW. Glutamate-induced retinal degeneration in neonatal mice: electron microscopy of the acutely evolving lesion. J Neuropathol Exp Neurol 1969;28:455–474.
74. Lipton SA. Molecular mechanisms of trauma-induced neuronal degeneration. Curr Opin Neurol Neurosurg 1993;6:588–596.
75. Dreyer EB, Grosskreutz CL. Excitatory mechanisms in retinal ganglion cell death in primary open angle glaucoma (POAG). Clin Neurosci 1997;4:270–273.
76. Dreyer EB, Lipton SA: New perspectives on glaucoma. JAMA 1999;281:306–308.
77. Dreyer EB, Zhang D, Lipton SA. Transcriptional or translational inhibition blocks low dose NMDA-mediated cell death. Neuro Report 1995;6:942–944.
78. Vorwerk CK, Lipton SA, Zurakowski D. Chronic low dose glutamate is toxic to retinal ganglion cells: toxicity blocked by memantine. Invest Ophthalmol Vis Sci 1996;37:1618–1624.
79. Brooks DE, Barcia GA, Dreyer EB. Vitreous body glutamate concentration in dogs with glaucoma. Am J Vet Res 1997;58:864–867.
80. Dreyer EB, Zurakowski D, Schumer RA. Elevated glutamate in the vitreous body of humans and monkeys with glaucoma. Arch Ophthalmol 1996;114:299–305.
81. Zeevalk GD, Nicklas WJ. Evidence that the loss of the voltage-dependent Mg2+ block of the N-methyl-d-aspartate receptor underlies receptor activation during inhibition of neuronal metabolism. J Neurochem 1992;59:1211–1220.
82. Bonfoco E, Krainc D, Ankarcrona M, et al. Apoptosis and necrosis: two distinct events induced respectively by mild and intense insults with NMDA or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 1995;92:7162–7166.
83. Budd SL, Tenneti L, Lishnak T, Lipton SA. Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons. Proc Natl Acad Sci USA 2000;97:6161–6166.
84. Dawson VL, Dawson TM, Bartley DA. Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci 1993;13:2651–2661.
85. Dawson VL, Dawson TM, London ED. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci USA 1991;88:6368–6332. Brooks DE, Barcia GA, Dreyer EB. Vitreous body glutamate concentration in dogs with glaucoma. Am J Vet Res 1997;58:864–867.
86. Lipton SA, Choi Y-B, Pan Z-H. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 1993;364:626–632.
87. Okamoto S-I, Li Z, Ju C, Schölzke MN. Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosis. Proc Natl Acad Sci USA 2002;99:3974–3979.
88. Tenneti L, DEmilia DM, Troy CM, Lipton SA. Role of caspases in N-methyl-d-aspartate-induced apoptosis in cerebrocortical neurons. J Neurochem 1998;71:946–959.
89. Tenneti L, Lipton SA. Involvement of activated caspase-3-like proteases in N-methyl-d-aspartate-induced apoptosis in cerebrocortical neurons. J Neurochem 1000;74:134–142.
90. Kaul M, Garden GA, Lipton SA. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 2001;410:988-994.
91. Dreyer EB, Zurakowski D, Schumer RA, et al. Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Arch Ophthalmol 1996;114:299–305.
92. Brooks DE, Garcia GA, Dreyer EB, et al. Vitreous body glutamate concentration in dogs with glaucoma. Am J Vet Res 1997;58:864–867.
93. Sucher NJ, Wong LA, Lipton SA. Redox modulation of NMDA receptor-mediated Ca21 flux in mammalian central neurons. Neuroreport 1990;1:29–32.
94. Sucher NJ, Aizenman E, Lipton SA. N-methyl-D-aspartate antagonists prevent kainate neurotoxicity in rat retinal ganglion cells in vitro. J Neurosci 1991;11:966–971.
95. Hollman PC, Katan MB. Absorption, metabolism and heaith effects of dietery flavonoids in man. Biomed Pharmacother 1997;51:305-310.
96. Hollman PC, Katan MB. Dietary flavonoids: intack, health effects and bioavailability. Food Chem Toxicol 1999;37:937-942.
97. Hertog MGL, Hollman PCH. Potential health effrcts of the dietary flavonol quercetin. Eur J Clin Nutr 1996;50:63-71.
98. Hollman PC, van Trijp LM, Buysman MN, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997;418:152-156.
99. Hertog MG, Fesken EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoid and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993;342:1107-1101.
100. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 1995;155:381-386.
101. Middleton EJ Effect of plant flavonoids on immune and inflammatory cell function, Adv Exp Med Biol 1998;439:175-182.
102. Wang HK, Xia Y, Yang ZY, Natschke SL, Lee KH. Recent advances in discovery and development of flavonoids and their analogues as antitumor and anti-HIV agents. Adv Exp Med Biol 1998;439:191-225.
103. Knekt P, Jarvinen R, Seppanen R, Hellovaara M, Teppo L, Pukkala E, Aromaa A. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol 1997;146:223-230.
104. Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000;63:1035-1042.
105. Spencer JPE, Schroeter H, Crossthwaithe AJ, Kuhnle G, Williams RJ, Rice-Evans C. Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Free Radic Biol Med 2001;31:1139–1146.
106. Ishige K, Schubert D, Sagara Y. Flavonoids protect neuronal cells from oxidative
stress by three distinct mechanisms. Free Radical Biol Med 2001;30:433–446.
107. Hollman PC, Bijman MN, van Gameren Y, Cnossen EP, de Vries JH, katan MB. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 1999;31:569-573.
108. Olthof M, Hollman PCH, Vree TB, fatan MB. Bioavailabilities of quercetin-3-glucoside and quercetin-4’-glucoside do not differ in human. J Nutr 2000;130:1200-1203.
109. Hsiu SL Huang TY, Hou YC, Chin DH, Chao PDL. Comparsin of metabolic pharmacokinetics of naringin and naringenin in rabbits. Life Sci 2002;70:1481-1489.
110. Chang CW, Hsiu SL, Wu PP, Kuo SC, Chao PDL. HPLC assay of naringin and hesperidin in Chinese herbs and serum. J Food Drug Anal 1997;5:111-120.
111. Naderi GA, Asgary S, Sarraf-Zadegan N, Oroojy H, Afshin-Nia F. Antioxidant activity of three extracts of Morus nigra. Phytothe Res 2004;18:365-369.
112. Matsubara Y, Yusa T, Sawabe A, Iizuka Y, Takekuma S, Yoshida Y. Structures of new cyclic peptides in young unshiu (Citrus unshiu Marcov.), orange (Citrus sinensis Osbeck.) and amanatsu (Citrus natsudaidai) peelings. Agric Biol Chem 1991;55:2923-2929.
113. Chen G, Zhang L, Zhao J, Ye J. Determination of hesperidin and synephrine in Pericarpium Citri Reticulatae by capillary electrophoresis with electrochemical detection. Anal Bioanal Chem 2002;373:169-173.
114. Wang JF, Guo YX, Niu JZ, Liu J, Wang LQ, Li PH. Effects of Radix Puerariae flavones on liver lipid metabolism in ovariectomized rats. World J Gastroenterol 2004;10:1967-1970.
115. Alves D, Perez-Fons L, Estepa A, Micol V. Membrane-related effects underlying the biological activity of the anthraquinones emodin and barbaloin. Biochem Pharmacol 2004;68:549-561.
116. Mijatovic S, Maksimovic-Ivanic D, Radovic J, Popadic D, Momcilovic M, Harhaji L, Miljkovic D, Trajkovic V. Aloe-emodin prevents cytokine-induced tumor cell death: the inhibition of auto-toxic nitric oxide release as a potential mechanism. Cell Mol Life Sci 2004;61:1805-1815.
117.Lu HF, Sue CC, Yu CS, Chen SC, Chen GW, Chung JG. Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells. Food Chem Toxicol 2004;42:1543-1552.
118. Lee YM, Wu TH, Chen SF, Chung JG. Effect of 5-methoxypsoralen (5-MOP) on cell apoptosis and cell cycle in human hepatocellular carcinoma cell line. Toxicol in Vitro 2003;17:279-287.
119. Chung JG, Yeh KT, Wu SL, Hsu NY, Chen GW, Yeh YW, Ho HC. Novel transmembrane GTPase of non-small cell lung cancer identified by mRNA differential display. Cancer Res 2001;61:8873-8879.
120. Park EK, Kwon KB, Park KI, Park BH, Jhee EC. Role of Ca+2 in diallyl disulfide-induced apoptotic cell death of HCT-15 cells. Exp Mol Med 2002;34:250-257.
121.Hehner SP, Heinrich M, Bork PM, Vogt M, Ratter F, Lehmann V, Schulze-Osthoff K, Droge W, Schmitz ML. Sesquiterpene lactones specifically inhibit activation of NF-kappa B by preventing the degradation of I kappa B-alpha and I kappa B-beta. J Biol Chem 1998;273:1288–1297.
122.Terry, D.E., Umstot E. and Desiderio D.M. Optimized sample-processing time and peptide recovery for the mass spectrometric analysis of protein digests. J Am Soc Mass Spectrom 2004;15:784-794.
123. Hirosawa, M., Hoshida, M.,Ishikawa, M., Toya, T. Comput. Appl. Biosci. 1993;9:161-167.
124. Kwong JM, Lam TT. N -methyl- D -aspartate (NMDA) induced apoptosis in adult rabbit retinas. Experimental eye research 2000;71:437-444.
125. Livak, K.J., Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25:402-408.
126. Keirsebilck A, Van Hoorde L, Gao Y, De Bruyne G, Bruyneel E, Vermassen P, Mareel M, van Roy F. Mechanisms of downregulation of transfected E-cadherin cDNA during formation of invasive tumors in syngeneic mice. Invasion and Metasis 1998;18:44-56.
127. Fu L, Benchimol S. Participation of the human p53 3’UTR in translational repression and activation following γ-irradiation 1997;16:4117-4125.
128. Lee Wy, Loflin P, Clancey CJ, Peng H, Lever JE. Cyclic nucleotide regulation of Na+/glucose cotransporter (SGLT1) mRNA stability. Interaction of a nucleocytoplamic protein with a regulatory domain in the 3’-untranslated region crital for stabilization. 2000;275:33998-34008.
129. Nathanson JA. Nitric oxide and nitrovasodilators in the eye: Implication for ocular physiology and glaucoma. J Glaucoma 1993;2:206-210.
130. Schuman JS, Erickson K, Nathanson JA. Nitrovasodilator effects on intraocular pressure and outflow facility in monkeys. Exp Eye Res 1994;58:99-105.
131. Nathanson JA, McKee M. Alterations of ocular nitric oxide synthase in human glaucoma. Invest Ophthalmol Vis Sci 1995;36:1774-1784.
132. Haefliger IO, Dettmann E, Liu R, Meyer P, Prunte C, Messerli J, Flammer J. Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma. Surv Ophthalmol Suplement 1999;1:S51-S58.
133.Chang CJ, Chiang CH, Chow JC, Lu DW. Aqueous humor nitric oxide levels differ in patients with different types of glaucoma. J Ocul Pharmacol Ther 2000;5:399-406.
134. Galassi F, Sodi A, Ucci F, Renieri G, Pieri G, Masini E. Ocular dynamics and nitric oxide in normal pressure glaucoma. Acta Ophthalmol Scand Supplement 2000;78:37-38.
135. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:209-242.
136. Anderson RE, Maude MB. Phospholipids of bovine outer segments. Biochemistry 1970;9:3264-3268
137. Murphy MP. Nitric oxide and cell death. Biochim Biophys Acta 1999;1411:401-414.
138. Hangai M., Yoshimura N, Hiroi K, Mandai M, Honda Y. Inducible nitric oxide synthase in retinal ischemia-reperfusion injury. Exp Eye Res 1996;63:501-519.
139. Oku H, Yamaguchi H, Sugiyama T, Kojima S, Ota M, Azuma I. Retinal toxicity of nitric oxide released by administration of a nitric oxide donor in the albino rabbit. Invest Ophthalmol Vis Sci 1997;38:2540-2544.
140. Beckman JS, Chen J, Ischiropoulos H, Crow JP. Oxidative chemistry of peroxynitrite. Methods Enzymol 1994;233:229-240.
141. Koss MC. Functional role of nitric oxide in regulation of ocular blood flow. Eur J Pharmacol 1999;374:161-174.
142. Nathanson JA. Nitrovasodilators as a new class of ocular hypotensive agents. J Pharmacol E Ther 1992;260:956-965.
143. Kubota R, Noda S, Wang Y, Minoshima S, Asakawa S, Kudoh J, Mashima Y, Oguchi Y, Shimizu N. A novel myosin-like protein (myocilin) expressed in the connecting cilium of photoreceptor molecular cloning, tissue expression, and chromosomal mapping. Genomico 1997;41:360-369.
144. Takahashi H, Noda S, Imamura Y, Nagasawa A, Kubota R, Mashima Y, Kudoh J, Oguchi Y, Shimizu N. Mouse myocilin (Myoc) gene expression in ocular tissues.
Biochem Biophys Res Commun. 1998;248:104-109.
145. Mijatovic S, Maksimovic-Ivanic D, Radovic J, Popadic D, Momcilovic M, Harhaji L, Miljkovic D, Trajkovic V. Aloe-emodin prevents cytokine-induced tumor cell death: the inhibition of auto-toxic nitric oxide release as a potential mechanism. Cell Mol Life Sci. 2004;61:1805-1815.
146. Liang JW, Hsiu SL, Wu PP, Chao PDL. Emodin pharmacokinetics in rabbits. Planta Medica 1995;61:406-408.
147. Hsiu SL, Huang TY, Hou YC, Chin DH, Chao PDL. Comparsin of metabolic pharmacokinetics of naringin and naringenin in rabbits. Life Science 2002;70:1481-1489.
148. Fang SH, Hou YC, Chang WC, Hsiu SL, Chao PDL, Chiang BL. Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Science 2003;74,:743-756.
149. Yang JH, Hsia TC, Kuo HM, Chao PD, Chou CC, Wei YH, Chung JG. Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis. Drug Metab Dispos. 2006;34:296-304.
150. Olney JW, Ho OL. Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine. Nature 1970;227:609-611.
151. Lipton SA, Rosenberg RA. Mechanisms of disease: Excitatory amino acids as a final common pathway in neurologic disorders. N Engl J Med 1994;330:613–622.
152. Lesnikov VA, Abbasi N, Lesnikova MP, Lazaro CA, Campbell JS, Fausto N, Deeg HJ. Protection of human and murine hepatocytes against Fas-induced death by transferrin and iron. Apoptosis 2006;11:79-87.
153. Calabrese V. Highlight Commentary on "Redox proteomics analysis of oxidatively modified proteins in G93A-SOD1 transgenic mice-A model of familial amyotrophic lateral sclerosis". Free Radic Biol Med 2007;43:160-162.
154. Witt AE, Hines LM, Collins NL, Hu Y, Gunawardane RN, Moreira D, Raphael J, Jepson D, Koundinya M, Rolfs A, Taron B, Isakoff SJ, Brugge JS, LaBaer J. Functional proteomics approach to investigate the biological activities of cDNAs implicated in breast cancer. J Proteome Res 2006;5:599-610.
155. Lovegrove C. Galectin-1: a novel hypoxia-induced protein linked with tumor immune privilege. Nat Clin Pract Oncol 2006;3:6.
156. Tomlinson VA, Newbery HJ, Wray NR, Jackson J, Larionov A, Miller WR, Dixon JM, Abbott CM. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours. BMC Cancer 2005;5:113.
157. Rylander MN, Feng Y, Bass J, Diller KR. Thermally induced injury and heat-shock protein expression in cells and tissues. Ann N Y Acad Sci 2006;1066:222-242.
158. Zhang HW, Wang FS, Shao W, Zheng XL, Qi JZ, Cao JC, Zhang TM. Biochemistry (Mosc). Characterization and stability investigation of cu,zn-superoxide dismutase covalently modified by low molecular weight heparin. 2006;71:96-100.
159. Okada SF, O'Neal WK, Huang P, Nicholas RA, Ostrowski LE, Craigen WJ, Lazarowski ER, Boucher RC. Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell volume regulation in murine cells. J Gen Physiol. 2004;124:513-526.
160. Myung JK, Gulesserian T, Fountoulakis M, Lubec G. Deranged hypothetical proteins Rik protein, Nit protein 2 and mitochondrial inner membrane protein, Mitofilin, in fetal Down syndrome brain Cell Mol Biol (Noisy-le-grand) 2003;49:739-746.
161. Ciaffi M, Paolacci AR, D'Aloisio E, Tanzarella OA, Porceddu E. Cloning and characterization of wheat PDI (protein disulfide isomerase) homoeologous genes and promoter sequences. Gene 2006;366:209-218.
162. Ben Simon GJ, Bakalash S, Aloni E, Rosner M. A Rat Model for Acute Rise in intraocular pressure: immune modulation as a therapeutic strategy. Am J Ophthalmol 2006;141:1105-1111.
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