Please use this identifier to cite or link to this item:
http://hdl.handle.net/10553/50819
Title: | Regulation of the expression of prostate apoptosis response protein 4 (Par-4) in rat granulosa cells | Authors: | González, Inmaculada Hernández Santana, Pino Gonzalez-Robayna, Ignacio Ferrer, Milagros Morales, Victoria López Blanco, Félix Fanjul, Luisa F. |
UNESCO Clasification: | 32 Ciencias médicas 3205 Medicina interna |
Keywords: | Protein-Kinase-C Prostate Apoptosis Response-4 Ventral Prostate Follicular Atresia Down-Regulation, et al |
Issue Date: | 2007 | 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 |
Appears in Collections: | Artículos |
Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.