| Follicle-stimulating hormone regulates Pro-apoptotic protein Bcl-2-interacting mediator of cell death-extra long (BimEL) induced porcine granulosa cell apoptosis. | |
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MedLine Citation:
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PMID: 22235114 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The pro-apoptotic protein Bim (Bcl-2 [B-cell lymphoma-2] interacting modulator of cell death) has recently been identified and shown to promote cell death in response to several stimuli. In this report, we investigated the role of Bim in porcine follicular atresia. Initially, Bim cDNA was cloned and characterized from porcine ovarian tissue. Procine Bim had three alternative splicing variants (Bim-extra long, Bim-long and Bim-short), all containing the consensus Bcl-2 homology 3 (BH3) domain. We then found the Bim-extra long (BimEL) protein, the most abundant isoform of Bim, was strongly expressed and co-localized with apoptotic (TUNEL-positive) granulosa cells from porcine atretic follicles. Furthermore, over-expression of BimEL triggered apoptosis in granulosa cells. In primary granulosa cells cultures under basal conditions, we observed that BimEL expression was dampened by treatment with follicle-stimulating hormone (FSH). The role of the PI3K/Akt pathway in the regulation of repression was clarified by the use of the PI3K inhibitor, LY294002, and by transfection with Akt siRNA. Forkhead Box Protein O3a (FoxO3a), a well-defined transcriptional activator of Bim, was phosphorylated at Ser253 and inactivated after FSH stimulation. Also, FSH abolished FoxO3a nuclear accumulation in response to LY294002. Finally, chromatin immunoprecipitation (ChIP) assays demonstrated that FoxO3a directly bound and activated bim promoter. Taken together, we conclude that BimEL induces porcine granulosa cell apoptosis during follicular atresia and its expression is regulated by FSH via the PI3K/Akt/FoxO3a pathway. |
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Authors:
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Xian-Long Wang; Yi Wu; Lu-Bin Tan; Zhen Tian; Jing-Hao Liu; De-Sheng Zhu; Shen-Ming Zeng |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-10 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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China Agricultural University, China; |
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