2.3.2 白介素1β转化酶
一簇细胞凋亡蛋白酶,在细胞凋亡过程中起“刽子手”的作用,按其发现先后,分别被命名为caspase 1~12,均属于半胱氨酸蛋白酶,是直接导致凋亡细胞解体的蛋白酶系统,其活化是使效应细胞发生凋亡的中心环节。在凋亡的线粒体途径中,caspase9是最重要的起始因子;caspase3属于凋亡效应亚类,是细胞凋亡过程中最重要的终末执行酶[15],所以下调其表达有助于抑制晶状体上皮细胞凋亡,Yao等[16]在探讨Epigallocatechin gallate (EGCG,绿茶的主要成分)对过氧化氢诱导的人晶状体上皮细胞凋亡的保护作用时发现:EGCG能减少线粒体释放细胞色素C,并抑制由过氧化氢造成的caspase9,caspase3表达增强和Bcl2/Bax比值降低,从而抑制晶状体上皮细胞凋亡。细胞凋亡的三种途径并非完全独立地发挥作用,它们联系紧密,最终都集中到线粒体上完成凋亡过程。例如,当Ca2+从内质网中释放时,胞质中Ca2+负载,造成内质网腔内钙稳态的改变,继而产生内质网应激反应,触发了包括Bid,Bim,caspase8,12,JNK和Bax,Bad等在内的多种凋亡相关蛋白的表达才最终激活凋亡执行分子caspase3,从而导致细胞凋亡[17,18]。目前研究结果也显示晶状体上皮细胞凋亡的途径是与此类似的多基因参与、多途径的复杂过程。
目前,关于晶状体上皮细胞凋亡基因调控的研究主要集中在不同药物对不同致凋亡因素诱导的晶状体上皮细胞凋亡的作用观察以及对bcl2,bax和caspase等部分基因表达的影响,这些研究证实了部分凋亡相关基因对晶状体上皮细胞凋亡的调节作用,但对于其具体调节途径、相互关系以及是否还有其他基因参与调控尚待进一步研究,以更深入地探讨白内障的发病机制,为白内障防治提供更多的理论依据。
【参考文献】 1 Li WC, Kuszak JR, Dunn K, et al. Lens epithelial cell apoptosis appears to be a common cellular basis for noncongenital cataract development in humans and animals. J Cell Biol 1995;130(1):169181
2 Ifandi V, AlRubeai M. Regulation of cell proliferation and apoptosis in CHOK1 cells by the coexpression of cMyc and Bcl2. Biotechnol Prog 2005;21(3):671677
3 Hann SR. Role of posttranslational modifications in regulating cMyc proteolysis, transcriptional activity and biological function. Semin Cancer Biol 2006;16(4):288302
4 Long AC, Colitz CM, Bomser JA. Apoptotic and necrotic mechanisms of stressinduced human lens epithelial cell death. Exp Biol Med (Maywood) 2004;229(10):10721080
5 Yao K, Zhang L, Zhang Y, et al. The flavonoid, fisetin, inhibits UV radiationinduced oxidative stress and the activation of NFkappaB and MAPK signaling in human lens epithelial cells. Mol Vis 2008;14:18651871
6 MacEwan DJ. TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 2002;14(6):477492
7 Li J, Sharma R, Patrick B, et al. Regulation of CD95 (Fas) expression and Fasmediated apoptotic signaling in HLE B3 cells by 4hydroxynonenal. Biochemistry 2006;45(40):1225312264
8 Hueber A, Eichholtz CD, Kociok N, et al. Lens epithelial cells express CD95 and CD95 ligand treatment induces cell death and DNA fragmentation in vitro. Eur J Ophthalmol 2003;13(3):241245
9 Szegezdi E, Logue SE, Gorman AM, et al. Mediators of endoplasmic reticulum stressinduced apoptosis. EMBO Rep 2006;7(9):880885
10 Momoi T. Caspases involved in ER stressmediated cell death. J Chem Neuroanat 2004;28(12):101105
11 杨雪莉, 蔡可丽, 高雪,等.未折叠蛋白应答在晶状体上皮细胞凋亡中的作用. 山东大学学报医学版2008;46 (1):5256
12 ShoshanBarmatz V, Israelson A, Brdiczka D, et al. The voltagedependent anion channel (VDAC): function in intracellular signalling, cell life and cell death. Curr Pharm Des 2006;12(18):22492270
13 Wu ZM, Yin XX, Ji L, et al. Ginkgo biloba extract prevents against apoptosis induced by high glucose in human lens epithelial cells. Acta Pharmacol Sin 2008;29(9):10421050
14 黄秀榕,祁明信,汪朝阳,等.复方水蛭滴眼液抑制大鼠晶状体上皮细胞凋亡及其对Bcl2和Bax基因的调控.中西医结合学报 2007; 5(6):681685
15 Gupta S, Knowlton AA. HSP60, Bax, apoptosis and the heart. J Cell Mol Med 2005;9(1):5158
16 Yao K, Ye P, Zhang L, et al. Epigallocatechin gallate protects against oxidative stressinduced mitochondriadependent apoptosis in human lens epithelial cells. Mol Vis 2008;31(14):217223
17 Xu C, BaillyMaitre B, Reed JC. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 2005;115(10):26562664
18 Zhang K, Kaufman RJ. The unfolded protein response: a stress signaling pathway critical for health and disease. Neurology 2006;66(2 Suppl 1):S102109
上一页 [1] [2] |