|
5展望
老化和一些年龄相关性疾病中，均存在蛋白质的翻译后修饰，蛋白质去折叠，最终导致蛋白质凝聚，这被称为构象性疾病［37］.这组疾病有类似的病因，既均与老化相关.它包括淀粉病（Alzheimer病、全身淀粉样变性、Down综合征等）、朊病毒病(CJD vCJD BSE，Kuru) 、Huntington病、Alexander病和白内障.相同的病因，类似的发病机制，很可能存在相同的治疗方法.例如，因为谷胱甘肽(GSH)在各种白内障中均降低，提高晶状体中的GSH已被用于治疗白内障.同样提高GSH也已成为年龄相关性神经变性疾病Alzheimer病的治疗策略［38］.阿斯匹林类药物治疗Alzheimer病、白内障、心肌缺血、中风和各种肿瘤的临床资料也有力的支持了这种推测［14］
英国牛津大学眼科的最新研究成果显示α晶体蛋白和含巯基的还原剂共同作用，可使人白内障晶状体中活性已丧失的酶‘起死回生’［27］.α晶状体蛋白和硫甲丙脯酸使谷胱甘肽还原酶活性‘回升’79%，α晶状体蛋白和二硫苏糖醇使巯醇转移酶活性增加200%.这进一步揭示了α晶体蛋白的分子伴侣活性在维持晶状体代谢中的重要性，同时也为白内障的治疗提供了全新的思路.分子伴侣可‘解救’一类由于蛋白质错误折叠累积导致的构象性疾病，首次临床应用药物性伴侣治疗构象性疾病已取得可喜结果［40］.我们期待着白内障药物治疗研究的突破.
【参考文献】
［1］ Harding JJ. Cataract: Biochemistry, Epidemiology and Pharmacology ［M］. London, Chapwan and hall,1991:25-134.
［2］ West SK, Munoz B, Istre J, et al. Mixed lens opacities and subsequent mortality ［J］. Arch Ophthalmol, 2001;119(10):1562-1567.
［3］ Krag S, Olsen T, Andreassen T. Biomechanical characteristics of the human anterior lens capsule in relation to age ［J］. Invest Ophthalmol Vis Sci, 1997;38:357-342.
［4］ Bron AJ, Vrensen GFJM, Koretz J, et al. The ageing lens ［J］. Ophthalmologica, 2000;214:86-103.
［5］ GuggenmoosHoizmann I, Engel B, Henke V, et al. Cell density of human lens epithelium in women higher than in men ［J］. Invest Ophthalmol Vis Sci, 1989;30:330-338.
［6］ Konofsky K, Naumann GOH, GuggenmoosHoizmann I. Cell density and sex chromatin in lens epithelium of human cataract ［J］. Ophthalmology, 1987;94:875-881.
［7］ Karim AK, Jacob TJ, Thompson GM. The human anterior lens capsular: Cell density;morphology and mitotic index in normal and cataract lens ［J］. Exp Eye Res, 1987;45:865-870.
［8］ Harocopos GJ, Alvares KM, Koller AE, et al. Human agerelated cataract and lens epithelial cell death ［J］. Invest Ophthalmol Vis Sci, 1998;39:2696-2701.
［9］ Oharazawa H, Ibaraki N, Matsui H, et al. Agerelated changes of human lens epithelial cells in vivo ［J］. Ophthalmic Res, 2001;33:363-369.
［10］ Balaram M, Tung WH, Kuszak JR, et al. Noncontact specular microscopy of human lens epithelium ［J］. Invest Ophthalmol Vis Sci, 2000;41:474-479.
［11］ Li WC, Spector A.Lens epithelial cell apoptosis is an early event in the development of UVBinduced cataract ［J］. Free Radic Biol Med,1996;20:301-307.
［12］ Garner B, Vazquez S, Griffith R, et al. Identification of glutathionyl3hydroxynurenine glucoside as a novel fluorophore associated with ageing of the human lens ［J］. J Biol Chem, 1999;274:20847-20851.
［13］ Garner B, Roberg K, Qian M, et al. Distribution of ferritin and redoxactive transition metals in normal and cataractous human lenses ［J］. Exp Eye Res, 2000;71(6):599-604.
［14］ Harding JJ. Viewing molecular mechanisms of ageing through a lens ［J］. Ageing Res Rev, 2002;1:465-479.
［15］ Dovrat A, Scharf L, Eisenbach L, et al. G6PD molecules devoid of catalytic activity are present in the nucleus of the rat lens ［J］. Exp Eye Res, 1986;42:489.
［16］ Yan H, Harding JJ. Inactivation and loss of antigenicity of esterase by sugars and a steroid ［J］. Biochim Biophys Acta, 1999;1454(2):183-190.
［17］ Yan H, Harding JJ. Glycationinduced inactivation and loss of antigenicity of catalase and superoxide dismutase ［J］. Biochem J, 1997;328:599-605.
［18］ Yan H, Harding JJ. The molecular chaperone, αcrystallin, protects against loss of antigenicity and activity of esterase caused by sugars, sugar phosphate and a steroid ［J］. Biol Chem, 2003;384(8):1185-1194.
［19］ Ma Z, Hanson SRA, Lampi KJ, et al. Agerelated changes in human lens crystallins identified by HPLC and mass spectrometry ［J］. Exp Eye Res, 1998;67:21-27.
［20］ Lampi KJ, Ma ZX, Hanson SRA, et al. Agerelated changes in human lens crystallins identified by twodimensional electrophoresis and mass spectrometry ［J］. Exp Eye Res, 1998;67:31-34.
［21］ Srivastava OP, Srivastava K. BetaB2crystallin undergoes extensive truncation during aging in human lenses ［J］. Biochem Biophys Res Commun, 2003;301(1):44-52.
［22］ Yang Z, Chamorro M, Smith DL, et al. Identification of the major components of the high molecular weight crystallins from old human lenses ［J］. Curr Eye Res, 1994;13(6):415-420.
［23］ 严宏，惠延年. α晶体蛋白分子伴侣活性在白内障发病中作用的研究进展［J］. 眼科学报, 2000;16(2):91-99.
Yan H, Hui YN. The recent progress on the role of alphacrystallin as a molecular chaperone in cataractogenesis ［J］. Eye Sci, 2000;16(2):91-96.
［24］ Feng J, Smith DL, Smith JB. Human lens betacrystallin solubility ［J］. J Biol Chem, 2000;275(16):11585-11593.
［25］ 严宏，惠延年，李明勇，等. α晶状体蛋白分子伴娘功能的初步研究［J］. 中华眼科杂志,2004;40(8):559-560.
Yan H, Hui YN, Li MY, et al. Primarily study of alphacrystallin acting as molecular chaperone ［J］. Chin J Ophthalmol, 2004;40(8):559-560.
［26］ 严宏，惠延年，范建国，等. 老化过程中α晶体蛋白分子伴侣活性的变化［J］. 眼科学报,2003;19(4):239-243.
Yan H, Hui YN, Fan JG, et al. Change of alphacrystallin acting as molecular chaperone activity with ageing ［J］. Eye Sci, 2003;19(4):239-243.
［27］ Schey KL,Little M,Fowler JG,et al. Characterization of human lens major intrinsic protein structure ［J］. Invest Ophthalmol Vis Sci, 2000;41(1):175-183.
［28］ Nagpal RC, Singh RC, Singh GP, et al. Total lactate dehydrogenase and its isoenzyme pattern in lens, aqueous humour, and serum in cases of senile cataract ［J］. Acta Ophthalmol, 1991;69(1):57-67.
［29］ Balog Z, Sikic J, Vojnikovic B, et al. Senile cataract and the absorption activity of cytochrome C oxidizes ［J］. Coll Antropol, 2001;25(Suppl):33-34.
［30］ Kamei A. Variation in the glycosidase activity of human lens during ageing and with advance of senile cataract［J］. Biol Pharm Bull, 1995;18(10):1450-1452.
［31］ Kamei A. Properties of partially purified esterase in human crystalline lens and variation in its enzyme activity during aging and with advance of senile cataract ［J］. Biol Pharm Bull,1996;19:1223-1226.
［32］ Dilsiz N, Okucu A, Atas M. Determination of calcium, sodium, potassium and magnesium concentrations in human senile cataractous lenses ［J］. Cell Biochem Func, 2000;18(4):259-263.
［33］ Bateman OA, Lubsem NH, Slingsby C. Association behavior of human betaB1crystallin and its truncated forms ［J］. Exp Eye Res, 2001;73(3):321-329.
［34］ Zhang ZL, David LL, Smith DL, et al. Resistance of human betaB2crystallin to in vivo modification ［J］. Exp Eye Res, 2001;73(2):203-212.
［35］ Spector A. Oxidative stressinduced cataract: Mechanism of action ［J］. FASEB J, 1995;9(12):1173-1179.
［36］ Truscott RJW. Agerelated nuclear cataract: A lens transport problem ［J］. Ophthalmic Res, 2000;32:185-191.
［37］ Carrell RW, Lomas DA. Conformational disease ［J］. Lancet, 1997;350:134-140.
［38］ Butterfield DA, Pocernich CB, Drake J. Elevated glutathione as a therapeutic strategy in Alzheimers disease ［J］. Drug Dev Res, 2002;56:428-433.
［39］ Rachdana D, Lou MF, Harding JJ. Revival of inactive glyceraldehyde 3phosphate dehydrogenase in human cataract lenses by reduction ［J］. Exp Eye Res, 2004;79(1):105-109.
［40］ Bunk S. Chaperones to the rescue ［J］. Scientist, 2002;11:21-23. 上一页 [1] [2] |
