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Autophagy Contributes to Oxidative Stress-Induced Apoptosis in Porcine Granulosa Cells

文献类型： 外文期刊

作者： Zhang, Jia-Qing 1 ; Ren, Qiao-Ling 1 ; Chen, Jun-Feng 1 ; Gao, Bin-Wen 1 ; Wang, Xian-Wei 3 ; Zhang, Zi-Jing 1 ; Wang, 1 ;

作者机构： 1.Henan Acad Agr Sci, Inst Anim Husb & Vet Sci, Zhengzhou 450002, Peoples R China

2.Henan Key Lab Farm Anim Breeding & Nutr Regulat, Zhengzhou 450002, Peoples R China

3.Henan Prov Anim Husb Gen Stn, Zhengzhou 450008, Peoples R China

关键词： Autophagy; Apoptosis; Porcine granulosa cells; Oxidative stress

期刊名称：REPRODUCTIVE SCIENCES （ 影响因子：3.06； 五年影响因子：3.109 ）

ISSN： 1933-7191

年卷期：

页码：

收录情况： SCI

摘要： Oxidative stress-induced granulosa cell (GC) death is a major cause of follicular atresia. As the major types of programmed cell death, autophagy and apoptosis have been observed in response to H2O2-mediated oxidative stress and have been demonstrated to be responsible for porcine GC death. To date, however, the cellular reactions linking autophagy to the apoptosis of porcine GC under oxidative stress are still poorly understood. Porcine GC were treated with H2O2, and autophagic flux was examined by western blotting. Cell viability and cell death assays were performed after cotreatment of porcine GC with autophagy activator (rapamycin) or inhibitor (3-methyladenine, 3-MA) together with H2O2. We revealed that short exposure (1-3 h) of porcine GC to H(2)O(2)dramatically increased autophagic flux (1.8- to 2.5-fold over that in the control), whereas 6-12 h prolonged treatment decreased autophagy but elevated the caspase-3 activity and GC apoptotic rate. Furthermore, we showed that pretreatment with rapamycin exacerbated H2O2-mediated cytotoxicity and caspase-3 activation but that 3-MA or siRNAs specific for Beclin 1 and Atg7 genes ameliorated H2O2-mediated GC apoptosis. Together, our results indicate that autophagy plays a pivotal role in H2O2-mediated porcine GC apoptosis. Importantly, we show that the early induction of autophagic flux contributes to oxidative stress-induced apoptosis in porcine GC. The results also suggest that regulating the autophagy response in porcine GC under oxidative stress might be a new strategy for abnormal follicular atresia.

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