Eccentric exercise induces nitric oxide synthase expression through nuclear factor-kappaB modulation in rat skeletal muscle.
This study aimed to investigate the effect of eccentric exercise on the expression of the different nitric oxide synthase (NOS) isoforms in rat deep vastus lateralis muscle. Twenty-four rats were allocated to four experimental groups: rested control group, acutely exercised group after an intermittent downhill protocol for 90 min, acutely exercised group treated with pyrrolidine dithiocarbamate (100 mg/kg ip) for 24 and 1 h before the acute exercise bout, and acutely exercised group with a previous submaximal eccentric training of 8 wk. Acutely exercised rats showed increased levels of protein tyrosine nitration, NF-kappaB binding, and phospho-I kappaB alpha content. A significant increase was observed in mRNA level and protein content of neuronal NOS, inducible NOS, and endothelial NOS. The binding of NF-kappaB to the NOS isoform promoters, measured by a chromatin immunoprecipitation assay, was undetectable in rested rats, whereas it was evident in acutely exercised animals. All of these effects were partially abolished by pyrrolidine dithiocarbamate treatment and by training. In summary, our findings provide a direct link between the NF-kappaB signaling cascade and NOS expression in skeletal muscle following eccentric exercise and suggest a modulation of the expression of the three NOS isoforms by this transcription factor.
Lima-Cabello
Elena
E
Institute of Biomedicine, University of León, 24071 León, Spain.
Cuevas
María J
MJ
Garatachea
Nuria
N
Baldini
Marta
M
Almar
Mar
M
González-Gallego
Javier
J
D000818:Animals; D001665:Binding Sites; D004790:Enzyme Induction; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D005082:Physical Exertion; D011401:Promoter Regions, Genetic; D011759:Pyrrolidines / Q000494:pharmacology; D052097:Quadriceps Muscle / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D000072000:NF-KappaB Inhibitor alpha; C020972:pyrrolidine dithiocarbamic acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat