@article{oai:tmdu.repo.nii.ac.jp:00000174,
 author = {Koushi, Masami and Koushi, Masami and 亀井, 美子 and Kamei, Yoshiko and 青山, 靖典 and Aoyama, Yasunori and 朝海, 怜 and Asakai, Rei and 滝澤, 登一郞 and Takizawa, Touichiro},
 issue = {4},
 journal = {Journal of Medical and Dental Sciences, Journal of Medical and Dental Sciences},
 month = {Dec},
 note = {Apoptosis of granulosa cells (GC) contributes to ovarian follicular atresia, and has been implicated to depend on the oxidant status of GC within follicles. Here, we investigated the effects of cAMP and prostaglandin E2 (PGE2) on sensitivity to oxidative stress using 4B2 cells with cAMP-dependent, steroidogenic and differentiated properties. This cell line was isolated from mouse GC co-transfected with genes for SV40 large T antigen and Ad4BP/SF1 transcription factor (Kamei et al. 2005). Treatment of serum-starved cells with 8-Br-cAMPcaused 30 to 40% of the cells to become polygonal within 2 h through actin rearrangement. Interestingly, H2O2 treatment showed that these polygonal cells were vulnerable to oxidative stress that led to cell death, which was inhibited by pretreatment with phalloidin, an F-actin stabilizing agent. Although PGE2 alone had no effect, cotreatment with PGE2 and 8-Br-cAMP completely inhibited the effects of 8-Br-cAMP on cell shape change and oxidative stress vulnerability through phosphatidylinositol 3-kinase (PI3K)-dependent manner. Notably, PGE2 and 8-Br-cAMP cooperated additively to increase progesterone secretion. These data suggest that cAMP signaling in GC may enhance oxidative stress risk through actin rearrangement, and PGE2 may reduce such risk through activating PI3K, while cooperating with cAMP signaling in steroidogenesis.},
 pages = {167--176},
 volume = {54},
 year = {2007}
}