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NOS isoform‐specific regulation of basal but not exercise‐induced mitochondrial biogenesis in mouse skeletal muscle
Author(s) -
Wadley G. D.,
Choate J.,
McConell G. K.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.141309
Subject(s) - enos , medicine , mitochondrial biogenesis , endocrinology , nitric oxide synthase , basal (medicine) , skeletal muscle , soleus muscle , citrate synthase , nitric oxide synthase type iii , biology , chemistry , nitric oxide , mitochondrion , biochemistry , enzyme , insulin
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.