PMID- 15515061 OWN - NLM STAT- MEDLINE DCOM- 20050425 LR - 20220316 IS - 1040-452X (Print) IS - 1040-452X (Linking) VI - 70 IP - 1 DP - 2005 Jan TI - Anti-apoptotic action of stem cell factor on oocytes in primordial follicles and its signal transduction. PG - 82-90 AB - Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti-apoptotic action of SCF and the potential signal transduction pathways were investigated. The apoptosis was evaluated by means of in situ 3'-end labeling. The expressions of proteins were analyzed with immunohistochemistry and Western blot. The data showed that SCF significantly prevented oocytes from apoptosis in the cultured organs. Addition of a specific pharmacological inhibitor of PI3K abolished the anti-apoptotic action of SCF while that of a MEK inhibitor did not. The phosphorylation of two mitogen activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the MAPK activation occurred only in theca cells. The expressions of apoptosis-related gene products, the Bcl-2 family proteins, in response to SCF treatment were also investigated. While SCF up-regulated the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, it did the opposite to the pro-apoptotic factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl-xL and Bax but not on Bcl-2. Therefore, it seemed that SCF initiated an anti-apoptotic signal starting from its membrane receptor c-kit to Bcl-2 family members through PI3K/AKT and other signaling cascades in the oocytes of primordial follicles. CI - (c) 2004 Wiley-Liss, Inc. FAU - Jin, Xuan AU - Jin X AD - State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. FAU - Han, Chun-Sheng AU - Han CS FAU - Yu, Fu-Qing AU - Yu FQ FAU - Wei, Peng AU - Wei P FAU - Hu, Zhao-Yuan AU - Hu ZY FAU - Liu, Yi-Xun AU - Liu YX LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Reprod Dev JT - Molecular reproduction and development JID - 8903333 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Stem Cell Factor) RN - 0 (protein kinase modulator) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Animals MH - Apoptosis/*drug effects/physiology MH - Female MH - Intracellular Signaling Peptides and Proteins/pharmacology MH - Oocytes/chemistry/*drug effects MH - Organ Culture Techniques MH - Ovarian Follicle/chemistry/*drug effects MH - Phosphatidylinositol 3-Kinases/metabolism/physiology MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation MH - Protein Serine-Threonine Kinases/analysis/antagonists & inhibitors/metabolism MH - Proto-Oncogene Proteins c-bcl-2/analysis/metabolism MH - Rats MH - *Signal Transduction/drug effects/physiology MH - Stem Cell Factor/*pharmacology/physiology EDAT- 2004/10/30 09:00 MHDA- 2005/04/26 09:00 CRDT- 2004/10/30 09:00 PHST- 2004/10/30 09:00 [pubmed] PHST- 2005/04/26 09:00 [medline] PHST- 2004/10/30 09:00 [entrez] AID - 10.1002/mrd.20142 [doi] PST - ppublish SO - Mol Reprod Dev. 2005 Jan;70(1):82-90. doi: 10.1002/mrd.20142.