Document Detail


Apoptosis of rat granulosa cells after staurosporine and serum withdrawal is suppressed by adenovirus-directed overexpression of prohibitin.
MedLine Citation:
PMID:  17038561     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prohibitin (Phb1) is a highly conserved mitochondrial protein that is associated with granulosa cell differentiation, atresia, and luteolysis. Although prohibitin has been implicated in the suppression of apoptosis in mammalian cells, its specific role in programmed cell death in granulosa cells is unknown. In the present study, we examined the role of prohibitin in mediating staurosporine (STS) and serum withdrawal induced apoptosis in undifferentiated rat granulosa cells. Treatment of granulosa cells isolated from immature rat ovaries with STS and/or serum withdrawal induced a rapid decrease in the transmembrane potential of mitochondria, resulting in increased prohibitin content and induced apoptosis in a time- and dose-dependent manner. Infection of granulosa cells with a Phb1 adenoviral construct resulted in overexpression of prohibitin that markedly attenuated the ability of STS and serum withdrawal to induce apoptosis via the intrinsic apoptotic pathway. To determine the site of action of Phb1, granulosa cells were transfected with a prohibitin-eGFP fusion construct, and the fusion protein expression patterns were analyzed by fluorescence microscopy and Western blot analysis of cell fractionated samples. These studies indicated that the prohibitin-eGFP fusion protein moved from the cytoplasm into the mitochondria. However, no prohibitin-eGFP fusion protein was observed in the nucleus in response to the STS-induced apoptotic stimulus. This result was corroborated by Western blot analysis with green fluorescent protein-specific antibody. Furthermore, the prohibitin-eGFP fusion protein also inhibited programmed cell death. These results provide evidence that prohibitin could serve an antiapoptotic role in undifferentiated granulosa cells.
Authors:
Indrajit Chowdhury; Wei Xu; Jonathan K Stiles; Anthony Zeleznik; Xuebiao Yao; Roland Matthews; Kelwyn Thomas; Winston E Thompson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-10-12
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-20     Completed Date:  2007-02-13     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  206-17     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynecology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Apoptosis / drug effects,  physiology*
Blood Proteins / pharmacology
Caspase 3 / metabolism
Cell Differentiation / physiology
Cells, Cultured
Cytochromes c / metabolism
Enzyme Inhibitors / pharmacology*
Female
Gene Expression / physiology
Granulosa Cells / cytology*,  drug effects,  physiology*
Membrane Potential, Mitochondrial / drug effects,  physiology
Mitochondria / physiology
Phosphatidylserines / metabolism
Rats
Rats, Sprague-Dawley
Repressor Proteins / genetics*
Staurosporine / pharmacology*
Transfection
Grant Support
ID/Acronym/Agency:
RR03034/RR/NCRR NIH HHS; U54HD41749/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/Enzyme Inhibitors; 0/Phosphatidylserines; 0/Repressor Proteins; 0/prohibitin; 62996-74-1/Staurosporine; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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