Murphy, Kate T, Medved, Ivan, Brown, Malcolm J, Cameron-Smith, David and McKenna, Michael ORCID: 0000-0001-9998-0093 (2008) Antioxidant treatment with N-acetylcysteine regulates mammalian skeletal muscle with Na+-K+-ATPase alpha gene expression during repeated contractions. Experimental Physiology, 93 (12). pp. 1239-1248. ISSN 0958-0670

Abstract

Exercise increases Na+–K+ pump isoform gene expression and elevates muscle reactive oxygen species (ROS).We investigated whether enhanced ROS scavenging induced with the antioxidant N-acetylcysteine (NAC) blunted the increase in Na+–K+ pump mRNA during repeated contractions in human and rat muscle. In experiment 1, well-trained subjects received saline or NAC intravenously prior to and during 45 min cycling. Vastus lateralis muscle biopsies were taken pre-infusion and following exercise. In experiment 2, isolated rat extensor digitorum longus muscles were pre-incubated without or with 10mm NAC and then rested or stimulated electrically at 60 Hz for 90 s. After 3 h recovery, muscles were frozen. In both experiments, the muscles were analysed for Na+–K+ pump α1, α2, α3, β1, β2 and β3 mRNA. In experiment 1, exercise increased α2 mRNA by 1.0-fold (P =0.03), but α2 mRNA was reduced by 0.40-fold with NAC (P =0.03). Exercise increased α3, β1 and β2 mRNA by 2.0- to 3.4-fold (P <0.05), but these were not affected by NAC (P >0.32). Neither exercise nor NAC altered α1 or β3 mRNA (P >0.31). In experiment 2, electrical stimulation increased α1, α2 and α3 mRNA by 2.3- to 17.4-fold (P <0.05), but these changes were abolished by NAC (P >0.07). Electrical stimulation almost completely reduced β1 mRNA but only in the presence of NAC (P <0.01). Neither electrical stimulation nor NAC altered β2 or β3 mRNA (P >0.09). In conclusion, NAC attenuated the increase in Na+–K+ pump α2 mRNA with exercise in human muscle and all α isoforms with electrical stimulation in rat muscle. This indicates a regulatory role for ROS in Na+–K+ pump α isoform mRNA in mammalian muscle during repeated contractions.

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