title: Effect of PGC-1α overexpression or silencing on mitochondrial apoptosis of goat luteinized granulosa cells.
abstract: During goat follicular development, abnormal expression of peroxisome proliferator- activated receptor gamma coactivator-1 alpha (PGC-1α) in granulosa cells (GCs) may contribute to follicular atresia with unknown regulatory mechanisms. In this study, we investigate the effect of ectopic expression or interference of PGC-1α on cell apoptosis of goat first passage granulosa cells (FGCs) in vitro. The results indicate that PGC-1α silencing by short hairpin RNA (shRNA) in goat FGCs significantly reduced mitochondrial DNA (mtDNA) copy number (P < 0.05), changed mitochondria ultrastructure, and induced cell apoptosis (P < 0.05). The transcription and translation levels of the apoptosis-related genes BCL-2-associated X protein (BAX), caspase 3, and caspase 9 were significantly up-regulated (P < 0.05, respectively). Moreover, the ratio of BAX/B-cell lymphoma 2 (BCL-2) was reduced (P < 0.05), and the release of cytochrome c (cyt c) and lactate dehydrogenase (LDH) was significantly enhanced (P < 0.05, respectively) in PGC-1α interference goat FGCs. Furthermore, the expression of anti-oxidative related genes superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx) and catalase (CAT) was down-regulated (P < 0.05, respectively) and the activity of glutathione/glutathione disulfide (GSH/GSSG) was inhibited (P < 0.05). While enforced expression of PGC-1α increased the levels of genes involved in the regulation of mitochondrial function and biogenesis, and enhanced the anti-oxidative and anti-apoptosis capacity. Taken together, our results reveal that lack of PGC-1α may lead to mitochondrial dysfunction and disrupt the cellular redox balance, thus resulting in goat GCs apoptosis through the mitochondria-dependent apoptotic pathway.
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.|College of veterinary medicine, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.
authors.forename: Guo-Min
authors.initials: GM
authors.lastname: Zhang
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.
authors.forename: Ming-Tian
authors.initials: MT
authors.lastname: Deng
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.
authors.forename: Yi-Xuan
authors.initials: YX
authors.lastname: Fan
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wan
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Nie
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, No.1 Weigang, Nanjing, China. caeet@njau.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: College of veterinary medicine, Nanjing Agricultural University, No.1 Weigang, Nanjing, China. leizh@njau.edu.cn.
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Lei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006041:Goats; D006107:Granulosa Cells / Q000473:pathology*; D034461:Luteinization; D008928:Mitochondria / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics* / Q000494:pharmacology*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
keywords: Apoptosis; Goat granulosa cells; Mitochondria; PGC-1α