AMPK regulation of mouse oocyte meiotic resumption in vitro
0301 basic medicine
Adenosine
Microinjections
Mouse oocytes
AMP-Activated Protein Kinases
Protein Serine-Threonine Kinases
Rosiglitazone
Mice
03 medical and health sciences
Multienzyme Complexes
Meiotic resumption
Animals
Biology
Molecular Biology
Cells, Cultured
0303 health sciences
AMP-activated protein kinase
500
Cell Biology
Ribonucleotides
Aminoimidazole Carboxamide
3. Good health
Mice, Inbred C57BL
Meiosis
Oocytes
Female
Thiazolidinediones
Pentostatin
Vidarabine
Compound C
Developmental Biology
DOI:
10.1016/j.ydbio.2005.11.039
Publication Date:
2006-01-27T16:35:07Z
AUTHORS (7)
ABSTRACT
We have previously shown that the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK), stimulates an increase in AMPK activity and induces meiotic resumption in mouse oocytes [Downs, S.M., Hudson, E.R., Hardie, D.G., 2002. A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. Dev. Biol, 245, 200-212]. The present study was carried out to better define a causative role for AMPK in oocyte meiotic maturation. When microinjected with a constitutively active AMPK, about 20% of mouse oocytes maintained in meiotic arrest with dibutyryl cAMP (dbcAMP) were stimulated to undergo germinal vesicle breakdown (GVB), while there was no effect of catalytically dead kinase. Western blot analysis revealed that germinal vesicle (GV)-stage oocytes cultured in dbcAMP-containing medium plus AICAR possessed elevated levels of active AMPK, and this was confirmed by AMPK assays using a peptide substrate of AMPK to directly measure AMPK activity. AICAR-induced meiotic resumption and AMPK activation were blocked by compound C or adenine 9-beta-d-arabinofuranoside (araA, a precursor of araATP), both inhibitors of AMPK. Compound C failed to suppress adenosine uptake and phosphorylation, indicating that it did not block AICAR action by preventing its metabolism to the AMP analog, ZMP. 2'-deoxycoformycin (DCF), a potent adenosine deaminase inhibitor, reversed the inhibitory effect of adenosine on oocyte maturation by modulating intracellular AMP levels and activating AMPK. Rosiglitazone, an anti-diabetic agent, stimulated AMPK activation in oocytes and triggered meiotic resumption. In spontaneously maturing oocytes, GVB was preceded by AMPK activation and blocked by compound C. Collectively, these results support the proposition that active AMPK within mouse oocytes provides a potent meiosis-inducing signal in vitro.
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