The FASEB Journal • Research Communication Acute exercise activates nuclear factor (NF)-B signaling pathway in rat skeletal muscle

ABSTRACT Two studies were performed to investi-gate the effects of an acute bout of physical exercise on the nuclear protein B (NF-B) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n6) was run on the treadmill at 25 m/min, 5 % grade, for 1 h or until exhaustion (Ex), and compared with a second group (n6) 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 (n6) 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-B binding and P50 protein content in muscle nuclear extracts compared with C rats. Cytosolic IB and IB kinase (IKK) contents were decreased, whereas phospho-IB and phospho-IKK contents were in-creased, comparing Ex vs. C. The exercise-induced activation of NF-B signaling cascade was partially abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and exaggerated the effects ob-served in Ex rats. In Study 2, the time course of exercise-induced NF-B activation was examined. High-est levels of NF-B binding were observed at 2 h postexercise. Decreased cytosolic IB and increased phosphor-IB content were found 0–1 h postexercise whereas P65 reached peak levels at 2–4 h. These data suggest that the NF-B signaling pathway can be acti-vated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant pro-duction. The cascade of intracellular events may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier (Pfluegers Arch