Prohibitin (PHB) acts as a potent survival factor against ceramide induced apoptosis in rat granulosa cells

LIFE SCIENCES

卷:89

Article

Olatinwo, Moshood³  Thomas, Kelwyn²  Thompson, Winston E.¹ 

[1] Morehouse Sch Med, Dept Obstet & Gynecol, Cooperat Reprod Sci Res Ctr, Atlanta, GA 30310 USA

[2] Morehouse Sch Med, Dept Anat & Neurobiol, Atlanta, GA 30310 USA

[3] Summit ObGyn, Natchitoches, LA USA

关键词: Prohibitin;    Granulosa cells;    Apoptosis;    Mitochondria;    Ceramide;   

DOI  :  10.1016/j.lfs.2011.06.022

来源: Elsevier

【 摘 要 】

Aim: Ceramide is a key factor in inducing germ cell apoptosis by translocating from cumulus cells into the adjacent oocyte and lipid rafts through gap junctions. Therefore studies designed to elucidate the mechanistic pathways in ceramide induced granulosa cell (GC) apoptosis and follicular atresia may potentially lead to the development of novel lipid-based therapeutic strategies that will prevent infertility and premature menopause associated with chemo and/or radiation therapy in female cancer patients. Our previous studies have shown that Prohibitin (PHB) is intimately involved in GCs differentiation, atresia, and luteolysis. Main methods: In the present study, we have examined the functional effects of loss-/gain-of-function of PHB using adenoviral technology in delaying apoptosis induced by the physiological ligand ceramide in rat GCs. Key findings: Under these experimental conditions, exogenous ceramide C-8 (50 mu M) augmented the expression of mitochondria! PHB and subsequently cause the physical destruction of GC by the release of mitochondrial cytochrome c and activation of caspase-3. In further studies, silencing of PHB expression by adenoviral small interfering RNA (shRNA) sensitized GCs to ceramide C8-induce apoptosis. In contrast, adenovirus (Ad) directed overexpression of PHB in GCs resulted in increased PHB content in mitochondria and delayed the onset of ceramide induced apoptosis in the infected GCs. Significance: Taken together. these results provide novel evidences that a critical level of PHB expression within the mitochondria plays a key intra-molecular role in GC fate by mediating the inhibition of apoptosis and may therefore, contribute significantly to ceramide induced follicular atresia. (C) 2011 Elsevier Inc. All rights reserved.

【 授权许可】

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