NOS isoform-specific regulation of basal but not exercise-induced mitochondrial biogenesis in mouse skeletal muscle

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Wadley, Glenn D, Choate, Julia and McConell, Glenn ORCID: 0000-0002-8572-9065 (2007) NOS isoform-specific regulation of basal but not exercise-induced mitochondrial biogenesis in mouse skeletal muscle. Journal of Physiology, 585 (1). pp. 253-262. ISSN 0022-3751


Nitric oxide is a potential regulator of mitochondrial biogenesis. Therefore, we investigated if mice deficient in endothelial nitric oxide synthase (eNOS−/−) or neuronal NOS (nNOS−/−) have attenuated activation of skeletal muscle mitochondrial biogenesis in response to exercise. eNOS−/−, nNOS−/− and C57Bl/6 (CON) mice (16.3 ± 0.2 weeks old) either remained in their cages (basal) or ran on a treadmill (16 m min−1, 5% grade) for 60 min (n = 8 per group) and were killed 6 h after exercise. Other eNOS−/−, nNOS−/− and CON mice exercise trained for 9 days (60 min per day) and were killed 24 h after the last bout of exercise training. eNOS−/− mice had significantly higher nNOS protein and nNOS−/− mice had significantly higher eNOS protein in the EDL, but not the soleus. The basal mitochondrial biogenesis markers NRF1, NRF2α and mtTFA mRNA were significantly (P< 0.05) higher in the soleus and EDL of nNOS−/− mice whilst basal citrate synthase activity was higher in the soleus and basal PGC-1α mRNA higher in the EDL. Also, eNOS−/− mice had significantly higher basal citrate synthase activity in the soleus but not the EDL. Acute exercise increased (P< 0.05) PGC-1α mRNA in soleus and EDL and NRF2α mRNA in the EDL to a similar extent in all genotypes. In addition, short-term exercise training significantly increased cytochrome c protein in all genotypes (P< 0.05) in the EDL. In conclusion, eNOS and nNOS are differentially involved in the basal regulation of mitochondrial biogenesis in skeletal muscle but are not critical for exercise-induced increases in mitochondrial biogenesis in skeletal muscle.

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Additional Information

Online ISSN: 1469-7793

Item type Article
DOI 10.1113/jphysiol.2007.141309
Official URL
Subjects Historical > FOR Classification > 0601 Biochemistry and Cell Biology
Historical > Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
Keywords ResPubID22060. nitric oxide synthase, mitochondrial biogenesis, NOS isoform, basal, mice, skeletal muscles
Citations in Scopus 54 - View on Scopus
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