RESUMO
BMP-4 and BMP-7 are associated with the suppression of granulosa cell apoptosis. LY294002 (PI3K inhibitor) or UCN-01 (PDK-1 inhibitor) increased the percentage of apoptotic cells in the granulosa cells treated with BMP-4 or BMP-7. The inhibitors of ERK and p38 (SB203580) did not increase the percentage of apoptotic cells in the granulosa cells treated with BMP-4 or BMP-7. Akt inhibitor did not induce apoptosis in the BMP-4-treated granulosa cells, whereas it did induce apoptosis of the BMP-7-treated granulosa cells. In the granulosa cells treated with BMP-4, the PKC inhibitor increased the percentage of apoptotic cells. Our data show that BMP-4 and BMP-7 are associated with granulosa cell survival via several non-Smad specific pathways: BMP-4 via the PI3K/PDK-1/PKC and BMP-7 via the PI3K/PDK-1/Akt.
Assuntos
Apoptose/fisiologia , Proteína Morfogenética Óssea 4/fisiologia , Proteína Morfogenética Óssea 7/fisiologia , Células da Granulosa/fisiologia , Animais , Apoptose/efeitos dos fármacos , Proteína Morfogenética Óssea 4/farmacologia , Proteína Morfogenética Óssea 7/farmacologia , Bovinos , Células Cultivadas , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Células da Granulosa/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Piruvato Desidrogenase Quinase de Transferência de Acetil , Estaurosporina/análogos & derivados , Estaurosporina/farmacologiaRESUMO
Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-beta family, are crucial factors in follicular growth and development in the mammalian ovary. In this study, we examined the effects of BMP-4 and BMP-7 on granulosa cell apoptosis. Here, we report that BMP-7 suppresses granulosa cell apoptosis by inhibiting the release of caspase-activated DNase (CAD) via a mechanism which does not appear to be associated with the mitochondrial pathway, whereas BMP-4 inhibits the release of CAD. Our data provide the first evidence that BMP-4 and BMP-7 may inhibit granulosa cell apoptosis via different pathways.