|Title:||Regulation of the expression of prostate apoptosis response protein 4 (Par-4) in rat granulosa cells||Authors:||González, Inmaculada Hernández
Blanco, Felix Lopez
Fanjul, Luisa F.
Prostate Apoptosis Response-4
Down-Regulation, et al
|Issue Date:||2007||Publisher:||1360-8185||Journal:||Apoptosis : an international journal on programmed cell death||Abstract:||The par-4 gene, directs the expression of a protein in the rat ventral prostate after apoptotic stimuli but not growth stimulatory, growth arresting or necrotic signals. Since Par-4 expression appears to be ubiquitous we investigated the possibility of Par-4 having a role in the rat ovary granulosa cells apoptotic death. Par-4 mRNA was detected by RT-PCR with oligonucleotides designed to prime Par-4 leucine zipper in the ovaries of 12 day old rats and reached the higher levels in 24 days old rats. In situ hybridization analysis revealed that Par-4 expression is restricted to granulosa cells. PMSG priming of 24 day old rats for 2 days greatly reduced Par-4 expression in granulosa cells as determined by in situ hybridization, RT-PCR of mRNA and protein immunodetection with Western blot. Granulosa cells placed in serum-fee culture, exhibited increased levels of Par-4 mRNA and protein, in good correlation with the degree of apoptosis. The culture-induced increases in Par-4 are significantly prevented by FSH. Transient transfection of granulosa cells with Par-4 leucine zipper domain that functions as a dominant-negative regulator of Par-4 activity resulted in lower rates of apoptosis while overexpression of the full length Par-4 counteracted FSH effects on apoptosis. Par-4 association with PKC zeta which is supposed to inhibit this kinase mediated antiapoptotic way is also prevented by FSH and, FSH antiapoptotic effects are counteracted by a PKC zeta specific inhibitor. These findings indicate that FSH by suppressing Par-4 expression in the ovary activates PKC zeta-dependent antiapoptotic pathway and suggest that Par-4 is part of the mechanism underlying granulosa cells apoptotic demise.||URI:||http://hdl.handle.net/10553/50819||ISSN:||1360-8185||DOI:||10.1007/s10495-006-0019-7||Source:||Apoptosis[ISSN 1360-8185],v. 12 (4), p. 769-779|
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