PMID- 25350560 OWN - NLM STAT- MEDLINE DCOM- 20160108 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 10 DP - 2014 TI - PKCdelta and theta possibly mediate FSH-induced mouse oocyte maturation via NOX-ROS-TACE cascade signaling pathway. PG - e111423 LID - 10.1371/journal.pone.0111423 [doi] LID - e111423 AB - In mammals, gonadotropins stimulate oocyte maturation via the epidermal growth factor (EGF) network, and the protein kinase C (PKC) signaling pathway mediates this process. Tumor necrosis factor-alpha converting enzyme (TACE) is an important protein responding to PKC activation. However, the detailed signaling cascade between PKC and TACE in follicle-stimulating hormone (FSH)-induced oocyte maturation in vitro remains unclear. In this study, we found that rottlerin (mallotoxin, MTX), the inhibitor of PKC delta and theta, blocked FSH-induced maturation of mouse cumulus-oocyte complexes (COCs) in vitro. We further clarified the relationship between two molecules downstream of PKC delta and theta and TACE in COCs: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and its products, reactive oxygen species (ROS). We proved that the respective inhibitors of NOX, ROS and TACE could block FSH-stimulated oocyte maturation dose-dependently, but these inhibitory effects could be reversed partially by amphiregulin (Areg), an EGF family member. Notably, inhibition of PKC delta and theta prevented FSH-induced translocation of two cytosolic components of NOX, p47phox and p67phox, to the plasma membrane in cumulus cells. Moreover, FSH-induced TACE activity in cumulus cells was decreased markedly by inhibition of NOX and ROS. In conclusion, PKC delta and theta possibly mediate FSH-induced meiotic resumption in mouse COCs via NOX-ROS-TACE signaling pathway. FAU - Chen, Qian AU - Chen Q AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. FAU - Zhang, Wenqiang AU - Zhang W AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. FAU - Ran, Hao AU - Ran H AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. FAU - Feng, Lizhao AU - Feng L AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. FAU - Yan, Hao AU - Yan H AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. FAU - Mu, Xinyi AU - Mu X AD - Department of histology and embryology, Chongqing medical university, Chongqing, People's Republic of China. FAU - Han, Yingying AU - Han Y AD - College of biological sciences and technology, Beijing Forestry University, Beijing, People's Republic of China. FAU - Liu, Wei AU - Liu W AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. FAU - Xia, Guoliang AU - Xia G AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. FAU - Wang, Chao AU - Wang C AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141028 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Acetophenones) RN - 0 (Amphiregulin) RN - 0 (Benzopyrans) RN - 0 (Isoenzymes) RN - 0 (Reactive Oxygen Species) RN - 9002-68-0 (Follicle Stimulating Hormone) RN - E29LP3ZMUH (rottlerin) RN - EC 1.6.- (NADH, NADPH Oxidoreductases) RN - EC 1.6.3.- (NADPH Oxidase 1) RN - EC 2.7.11.13 (Prkcq protein, mouse) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.13 (Protein Kinase C-delta) RN - EC 2.7.11.13 (Protein Kinase C-theta) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.86 (ADAM17 Protein) RN - EC 3.4.24.86 (Adam17 protein, mouse) SB - IM MH - ADAM Proteins/*metabolism MH - ADAM17 Protein MH - Acetophenones/chemistry MH - Amphiregulin/metabolism MH - Animals MH - Benzopyrans/chemistry MH - Body Weight MH - Cells, Cultured MH - Female MH - Follicle Stimulating Hormone/*metabolism MH - Isoenzymes/*metabolism MH - Meiosis MH - Mice MH - Microscopy, Fluorescence MH - NADH, NADPH Oxidoreductases/metabolism MH - NADPH Oxidase 1 MH - Oocytes/cytology/*drug effects/physiology MH - Phagocytosis MH - Protein Kinase C/*metabolism MH - Protein Kinase C-delta/*metabolism MH - Protein Kinase C-theta MH - Reactive Oxygen Species/metabolism MH - *Signal Transduction PMC - PMC4211700 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/10/29 06:00 MHDA- 2016/01/09 06:00 PMCR- 2014/10/28 CRDT- 2014/10/29 06:00 PHST- 2014/07/07 00:00 [received] PHST- 2014/09/25 00:00 [accepted] PHST- 2014/10/29 06:00 [entrez] PHST- 2014/10/29 06:00 [pubmed] PHST- 2016/01/09 06:00 [medline] PHST- 2014/10/28 00:00 [pmc-release] AID - PONE-D-14-30250 [pii] AID - 10.1371/journal.pone.0111423 [doi] PST - epublish SO - PLoS One. 2014 Oct 28;9(10):e111423. doi: 10.1371/journal.pone.0111423. eCollection 2014.