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Biological Sciences Faculty Research and Publications

AMPK

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A Requirement For Fatty Acid Oxidation In The Hormone-Induced Meiotic Maturation Of Mouse Oocytes, Deepa Valsangkar, Stephen Downs Aug 2013

A Requirement For Fatty Acid Oxidation In The Hormone-Induced Meiotic Maturation Of Mouse Oocytes, Deepa Valsangkar, Stephen Downs

Biological Sciences Faculty Research and Publications

We have previously shown that fatty acid oxidation (FAO) is required for AMP-activated protein kinase (PRKA)-induced maturation in vitro. In the present study, we have further investigated the role of this metabolic pathway in hormone-induced meiotic maturation. Incorporating an assay with 3H-palmitic acid as the substrate, we first examined the effect of PRKA activators on FAO levels. There was a significant stimulation of FAO in cumulus cell-enclosed oocytes (CEO) treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and RSVA405. In denuded oocytes (DO), AICAR stimulated FAO only in the presence of carnitine, the molecule that facilitates fatty acyl CoA entry into the …


Perturbing Microtubule Integrity Blocks Amp-Activated Protein Kinase-Induced Meiotic Resumption In Cultured Mouse Oocytes, Ru Ya, Stephen Downs Jan 2012

Perturbing Microtubule Integrity Blocks Amp-Activated Protein Kinase-Induced Meiotic Resumption In Cultured Mouse Oocytes, Ru Ya, Stephen Downs

Biological Sciences Faculty Research and Publications

The oocyte meiotic spindle is comprised of microtubules (MT) that bind chromatin and regulate both metaphase plate formation and karyokinesis during meiotic maturation; however, little information is known about their role in meiosis reinitiation. This study was conducted to determine if microtubule integrity is required for meiotic induction and to ascertain how it affects activation of AMP-activated protein kinase (AMPK), an important participant in the meiotic induction process. Treatment with microtubule-disrupting agents nocodazole and vinblastine suppressed meiotic resumption in a dose-dependent manner in both arrested cumulus cell-enclosed oocytes (CEO) stimulated with follicle-stimulating hormone (FSH) and arrested denuded oocytes (DO) stimulated …


Mouse Versus Rat: Profound Differences In Meiotic Regulation At The Level Of The Isolated Oocyte, Stephen Downs Oct 2011

Mouse Versus Rat: Profound Differences In Meiotic Regulation At The Level Of The Isolated Oocyte, Stephen Downs

Biological Sciences Faculty Research and Publications

Cumulus cell-enclosed oocytes (CEO), denuded oocytes (DO), or dissected follicles were obtained 44–48 hr after priming immature mice (20–23 days old) with 5 IU or immature rats (25–27 days old) with 12.5 IU of equine chorionic gonadotropin, and exposed to a variety of culture conditions. Mouse oocytes were more effectively maintained in meiotic arrest by hypoxanthine, dbcAMP, IBMX, milrinone, and 8-Br-cGMP. Atrial natriuretic peptide, a guanylate cyclase activator, suppressed maturation in CEO from both species, but mycophenolic acid reversed IBMX-maintained meiotic arrest in mouse CEO with little activity in rat CEO. IBMX-arrested mouse, but not rat, CEO were induced to …


Fatty Acid Oxidation And Meiotic Resumption In Mouse Oocytes, Stephen Downs, Jessica Odette, John Klinger Sep 2009

Fatty Acid Oxidation And Meiotic Resumption In Mouse Oocytes, Stephen Downs, Jessica Odette, John Klinger

Biological Sciences Faculty Research and Publications

We have examined the potential role of fatty acid oxidation (FAO) in AMP-activated protein kinase (AMPK)-induced meiotic maturation. Etomoxir and malonyl CoA, two inhibitors of carnitine palmitoyl transferase-1 (CPT1), and thus FAO, blocked meiotic induction in dbcAMP-arrested cumulus cell-enclosed oocytes (CEO) and denuded oocytes (DO) by the AMPK activator, AICAR. C75, an activator of CPT1 and FAO, stimulated meiotic resumption in CEO and DO. This effect was insensitive to the AMPK inhibitor, compound C, indicating an action downstream of AMPK. Palmitic acid or carnitine also promoted meiotic resumption in DO in the presence of AICAR. Since C75 also suppresses the …