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• W1542720596 abstract "Nitric oxide (NO) induces mitochondrial biogenesis in skeletal muscle cells via upregulation of the peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). Further, we have shown that nitric oxide interacts with the metabolic sensor enzyme, AMPK. Therefore, we tested the hypothesis that nitric oxide and AMPK act synergistically to upregulate PGC-1α mRNA expression and stimulate mitochondrial biogenesis in culture. L6 myotubes treated with nitric oxide donors, S-nitroso-N-penicillamine (SNAP, 25 μM) or diethylenetriamine-NONO (DETA-NO, 50 μM), exhibited elevated AMPK phosphorylation, PGC-1α mRNA and protein, and basal and uncoupled mitochondrial respiration (P < 0.05). Pre-treatment of cultures with the AMPK inhibitor, Compound C, prevented these effects. Knockdown of AMPKα1 in L6 myotubes using siRNA reduced AMPKα protein content and prevented upregulation of PGC-1α mRNA by DETA-NO. Meanwhile, siRNA knockdown of AMPKα2 had no effect on total AMPKα protein content or PGC-1α mRNA. These results suggest that NO effects on PGC-1α expression are mediated by AMPKα1. Paradoxically, we found that the AMPK-activating compound, AICAR, induced NO release from L6 myotubes, and that AICAR-induced upregulation of PGC-1α mRNA was prevented by inhibition of NOS with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mM). Additionally, incubation of isolated mouse extensor digitorum longus (EDL) muscles with 2 mM AICAR for 20 min or electrical stimulation (10 Hz, 13 V) for 10 min induced phosphorylation of AMPKα (P < 0.05), which was completely prevented by pre-treatment with the NOS inhibitor, L-N(G)-monomethyl arginine (L-NMMA, 1 mM). These data identify the AMPKα1 isoform as the mediator of NO-induced effects in skeletal muscle cells. Further, this study supports a proposed model of synergistic interaction between AMPK and NOS that is critical for maintenance of metabolic function in skeletal muscle cells." @default.
• W1542720596 created "2016-06-24" @default.
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• W1542720596 date "2010-09-15" @default.
• W1542720596 modified "2023-10-09" @default.
• W1542720596 title "Nitric oxide and AMPK cooperatively regulate PGC-1α in skeletal muscle cells" @default.
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• W1542720596 doi "https://doi.org/10.1113/jphysiol.2010.194035" @default.
• W1542720596 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2988518" @default.
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• W1542720596 hasPublicationYear "2010" @default.
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