Acetyl CoA Carboxylase and Meiotic Maturation in Mouse Oocytes.
Year: 2011
Type: conference-abstract
Abstract: AMP-activated protein kinase (AMPK) serves as a stress response kinase and cellular fuel gauge and has been shown to be important for resumption of maturation in mouse oocytes. Acetyl coenzyme A carboxylase (ACC), which serves as a negative regulator of fatty acid oxidation through the product malonyl CoA, is an important substrate of AMPK. By phosphorylating and thereby inactivating ACC, AMPK removes the block to fatty acid oxidation, an essential pathway for meiotic maturation. In the present study, we have examined a potential role for ACC in meiotic maturation. We tested the effect of two inhibitors, acting on different sites in the ACC molecule, on the in vitro maturation of cumulus cell-enclosed oocytes and denuded oocytes. Both inhibitors (Soraphen A and CP-640186) were found to dose-dependently overcome the meiotic arrest maintained by either the cAMP analog, dbcAMP, or the phosphodiesterase inhibitor, IBMX. These data suggest that AMPK activation can be bypassed in meiotic maturation by inactivating ACC, its downstream target. ACC localization was studied in both in vitro and in vivo induction systems. For the in vitro system, IBMX-arrested oocytes were stimulated to resume maturation by 1mM AICAR (an AMPK agonist) and were immunostained for phospho-ACC (pACC) at different stages of maturation. pACC was found to localize in the germinal vesicle in AICAR-treated oocytes, but not control oocytes. Following germinal vesicle breakdown, pACC also colocalized with condensed chromosomes and later moved to spindle poles at metaphases I and II. In vivo-maturing oocytes from hCG-injected mice displayed a similar localization pattern. Studies on localization of the phosphorylated ACC beta (pACC2) isoform showed a similar pattern to that of pan-pACC both in vivo as well as in vitro, suggesting that this mitochondria-associated isoform may be involved. Our results suggest that inactivation of ACC by AMPK-mediated phosphorylation removes the block to beta-oxidation and mediates meiotic induction. (poster)
Source: Biology of Reproduction
Authors: Deepa Valsangkar, Stephen M. Downs
Institution: Marquette University
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,605
OpenAlex ID: W2592958644