Acute exercise activates nuclear factor (NF)-κB signaling pathway in rat skeletal muscle

Two studies were performed to investigate the effects of an acute bout of physical exercise on the nuclear protein κB (NF-κB) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n=6) was run on the treadmill at 25 m/min, 5% grade, for 1 h or until exhaustion (Ex), and compared with a second group (n=6) injected with two doses of pyrrolidine dithiocarbamate (PDTC, 100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional groups of rats (n=6) were injected with either 8 mg/kg (i.p.) of lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline (C) and killed at resting condition. Ex rats showed higher levels of NF-κB binding and P50 protein content in muscle nuclear extracts compared with C rats. Cytosolic IκBα and IκB kinase (IKK) contents were decreased, whereas phospho-IκBα and phospho-IKK contents were increased, comparing Ex vs. C. The exercise-induced activation of NF-κB signaling cascade was partially abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and exaggerated the effects observed in Ex rats. In Study 2, the time course of exercise-induced NF-κB activation was examined. Highest levels of NF-κB binding were observed at 2 h postexercise. Decreased cytosolic IκBα and increased phosphor-IκBα content were found 0-1 h postexercise whereas P65 reached peak levels at 2-4 h. These data suggest that the NF-κB signaling pathway can be activated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant production. The cascade of intracellular events may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier.