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J Physiol Volume 585, Number 1, 253-262, November 15, 2007 DOI: 10.1113/jphysiol.2007.141309
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SKELETAL MUSCLE AND EXERCISE

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

G. D. Wadley1, J. Choate2 and G. K. McConell1

1 Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia
2 Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia

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, NRF2{alpha} 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-1{alpha} 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-1{alpha} mRNA in soleus and EDL and NRF2{alpha} 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.

(Received 25 July 2007; accepted after revision 25 September 2007; first published online 4 October 2007)
Corresponding author G. Wadley: Department of Physiology, University of Melbourne, Parkville, 3010, Australia. Email: gdwadley{at}unimelb.edu.au




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