Central role of nitric oxide synthase in AICAR and caffeine-induced mitochondrial biogenesis in L6 myocytes

Abstract

5-Aminoimidazole-4-carbox-amide-nbonucleoside (AICAR) and caffeine, which activate AMPactivated protein kinase (AMPK) and cause sarcoplasmic reticulum calcium release, respectively, have been, shown to increase mitochondrial biogenesis in L6 myotubes. Nitric oxide (NO) donors also increase mitochondrial biogenesis. Since neuronal and endothelial NO synthase (NOS) are calcium dependent and are also phosphorylated by AMPK, we hypothesized that NOS inhibition would attenuate the activation of mitochondrial biogenesis in response to AICAR and caffeine. L6 myotubes either were not treated (control) or were exposed acutely or for 5 h/day over 5 days to 100 μM of N G-nitro-L-arginine methyl ester (..