Bone morphogenetic protein (BMP)-4 and BMP-7 suppress granulosa cell apoptosis via different pathways: BMP-4 via PI3K/PDK-1/Akt and BMP-7 via PI3K/PDK-1/PKC.
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.
Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Inada-Machi, Obihiro, Hokkaido 080-8555, Japan. shimizut@obihiro.ac.jp
Takashi
T
Shimizu
Takefumi
T
Kayamori
Chiaki
C
Murayama
Akio
A
Miyamoto
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology / Q000502:physiology*; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D019311:Staurosporine / Q000031:analogs & derivatives / Q000494:pharmacology
D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D002867:Chromones; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D019311:Staurosporine; C525809:BMP4 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C054852:7-hydroxystaurosporine; C093642:SB 203580