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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (8): 23-26.doi: 10.6040/j.issn.1671-7554.0.2014.195

• 基础医学 • 上一篇    下一篇

线粒体靶向性肽SS-31对H2O2诱导人晶状体上皮细胞凋亡的保护作用

郭长艳1, 秦雪娇1, 吴晓莉2, 高雪3, 蔡可丽1   

  1. 1. 山东大学齐鲁医院眼科, 山东 济南 250012;
    2. 山东省荣军总医院眼科, 山东 济南 250013;
    3. 山东大学第二医院眼科, 山东 济南 250033
  • 收稿日期:2014-04-04 发布日期:2015-08-10
  • 通讯作者: 蔡可丽.E-mail:caikeli@163.com E-mail:caikeli@163.com
  • 基金资助:
    济南市科技发展计划(201102065)

Protective effect of mitochondria-targeted peptide SS-31 against H2O2-induced apoptosis in human lens epithelial cells

GUO Changyan1, QIN Xuejiao1, WU Xiaoli2, GAO Xue3, CAI Keli1   

  1. 1. Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Department of Ophthalmology, Shandong Rongjun Hospital, Jinan 250013, Shandong, China;
    3. Department of Ophthalmology, Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Received:2014-04-04 Published:2015-08-10

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摘要： 目的 研究线粒体靶向性肽SS-31在H2O2诱导的人晶状体上皮细胞凋亡中的保护作用及其分子机制.方法 体外培养人晶状体上皮细胞系SRA01/04,选取相同代次的SRA01/04细胞进行实验,应用100 μmol/L H2O2 构建凋亡模型,随机分为正常对照组、H2O2处理组、3个不同浓度的SS-31预处理组.应用MTT法检测各组细胞存活率;流式细胞术检测各组细胞凋亡率;Western blotting检测各组凋亡蛋白Bcl-2、Bax、Cleaved-Caspase-3的表达.结果 H2O2处理24 h后,细胞存活率降低,凋亡率升高,促凋亡蛋白Bax的表达升高,抗凋亡蛋白Bcl-2的表达降低,Bax/Bcl-2比率升高,Cleaved-Caspase-3的表达升高.SS-31预处理能明显提高细胞的存活率,且与浓度呈正相关.同时,SS-31还能减少细胞的凋亡率,下调Bax的表达,上调Bcl-2的表达,减少Cleaved-Caspase-3的激活,从而发挥抗凋亡作用.结论 SS-31能在H2O2诱导的人晶状体上皮细胞凋亡中有效地发挥保护作用,但能否应用于白内障治疗有待深入研究.

关键词: SS-31, 人晶状体上皮细胞, 氧化应激, 凋亡, 线粒体靶向性肽

Abstract: Objective To study the protective effect of SS-31 against H2O2-induced apoptosis in human lens epithelial cells and the possible mechanism. Methods SRA01/04 cells, an immortal human lens epithelial cell line, were cultured in vitro. SRA01/04 cells at the same generation were chosen and 100 μmol/L H2O2 was used to build the model of apoptosis. The cells were randomly allocated into five groups: the control group, the group treated by H2O2, and three groups pretreated by different concentrations of SS-31. The cell viabilities were monitored by using 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide(MTT) assay. The cell apoptotic rates were detected with Annexin V-Propidium iodide double-staining flow cytometry. The expressions of Bcl-2, Bax and Cleaved-Caspase-3 were tested by using Western blotting. Results After exposure of 100 μmol/L H2O2 for 24 h, the cell viabilities decreased, cell apoptotic rates increased, expression of pro-apoptotic protein Bax increased, expression of anti-apoptotic protein Bcl-2 decreased, and expression of Cleaved-Caspase-3 increased. Pretreatment of SS-31 at different concentrations improved cell viabilities in a dose-dependent manner. Meanwhile, SS-31 plays an anti-apoptotic role by decreasing cell apoptotic rate, down-regulating the expression of Bax, up-regulating the expression of Bcl-2, and suppressing the activation of Cleaved-Caspase-3. Conclusion SS-31 efficiently protects human lens epithelial cells against H2O2-induced apoptosis. Further studies are needed on whether SS-31 can be used in medicine treatment for cataract.

Key words: SS-31, Human lens epithelial cells, Apoptosis, Mitochondria-targeted peptide, Oxidative stress

中图分类号: 

  • R776.1
[1] Resnikoff S, Pascolini D, Etya'ale D, et al. Global data on visual impairment in the year 2002[J]. Bull World Health Organ, 2004, 82(11):844-851.
[2] Li WC, Kuszak JR, Dunn K, et al. Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals[J]. J Cell Biol, 1995, 130(1):169-181.
[3] Zhao K, Luo G, Giannelli S, et al. Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines[J]. Biochem Pharmacol, 2005, 70(12):1796-1806.
[4] Thomas DA, Stauffer C, Zhao K, et al. Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function[J]. J Am Soc Nephrol, 2007, 18(1):213-222.
[5] 葛坚.眼科学[M].北京:人民卫生出版社,2011:203.
[6] Jia ZY, Song Z, Liu P, et al. Grape seed proanthocyanidin extract protects human lens epithelial cells from oxidative stress via reducing NF-kB and MAPK protein expression[J]. Molecular Vision, 2011, 17:210-217.
[7] Babizhayev MA, Deyev AI, Yermakova VN, et al. Lipid peroxidation and cataracts: N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human and canine eyes[J].Drugs R D, 2004, 5(3):125-139.
[8] Long AC, Colitz CM, Bomser JA. Apoptotic and necrotic mechanisms of stress-induced human lens epithelial cell death[J]. Exp Biol Med (Maywood), 2004, 229(10):1072-1080.
[9] Yao H, Tang X, Shao X, et al. Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9[J]. Cell Res, 2007, 17(6):565-571.
[10] Spector A, Garner W H. Hydrogen peroxide and human cataract[J]. Exp Eye Res, 1981, 33(6):673-681.
[11] Manczaka M, Mao P, Calkins MJ, et al. Mitochondria-targeted antioxidants protect against amyloid-β toxicity in Alzheimer's disease neurons[J].J Alzheimer Dis, 2010, 20:609-631.
[12] Murphy MP, Smith RA. Drug delivery to mitochondria: the key to mitochondrial medicine[J]. Adv Drug Deliv Rev, 2000, 41(2):235-250.
[13] Smith RA, Porteous CM, Coulter CV, et al. Selective targeting of an antioxidant to mitochondria[J]. Eur J Biochem, 1999, 263(3):709-716.
[14] Petersen A, Zetterberg M, Sjostrand J, et al. Potential protective effects of NSAIDs/ASA in oxidatively stressed human lens epithelial cells and intact mouse lenses in culture[J]. Ophthalmic Res, 2005, 37(6):318-327.
[15] Ott M, Robertson JD, Gogvadze V, et al. Cytochrome c release from mitochondria proceeds by a two-step process[J]. Proc Natl Acad Sci U S A, 2002, 99(3):1259-1263.
[16] Liu X, Kim CN, Yang J, et al. Introduction of apoptotic program in cell-free extracts:requirement for dATP and cytochrome c[J]. Cell, 1996, 86(1):147-157.
[17] Fuchs Y, Steller H. Programmed cell death in animal development and disease[J].Cell, 2011, 147(4):742-758.
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