Eccentric exercise markedly increases c-Jun NH₂-terminal kinase activity in human skeletal muscle

Abstract

Eccentric contractions require the lengthening of skeletal muscle during force production and result in acute and prolonged muscle injury. Because a variety of stressors, including physical exercise and injury, can result in the activation of the c-Jun NH(2)-terminal kinase (JNK) intracellular signaling cascade in skeletal muscle, we investigated the effects of eccentric exercise on the activation of this stress-activated protein kinase in human skeletal muscle. Twelve healthy subjects (7 men, 5 women) completed maximal concentric or eccentric knee extensions on a KinCom isokinetic dynamometer (10 sets, 10 repetitions). Percutaneous needle biopsies were obtained from the vastus lateralis muscle 24 h before exercise (basal), immediately postexercise, and 6 h postexercise. Whereas both forms of exercise increased JNK activity immediately postexercise, eccentric contractions resulted in a much higher activation (15.4 +/- 4.5 vs. 3.5 +/- 1.4-fold increase above basal, eccentric vs. concentric). By 6 h after exercise, JNK activity decreased back to baseline values. In contrast to the greater activation of JNK with eccentric exercise, the mitogen-activated protein kinase kinase 4, the immediate upstream regulator of JNK, was similarly activated by concentric and eccentric exercise. Because the activation of JNK promotes the phosphorylation of a variety of transcription factors, including c-Jun, the results from this study suggest that JNK may be involved in the molecular and cellular adaptations that occur in response to injury-producing exercise in human skeletal muscle.

Characterization of contraction-inducible CXC chemokines and their roles in C2C12myocytes

“…These data indicate that differentiated C 2 C 12 myotubes possess cellular machinery/systems sufficient to transduce the contractile/elongation signals for activating the JNK-ATF2 signaling cascades, leading to rapid induction of these CXC chemokines, a phenomenon similar to that observed in vivo in skeletal muscle. In excellent agreement with our findings, physical exercise has been reported to immediately induce phosphorylation/activation of JNK and subsequent increases in the transcriptions of target genes in working skeletal muscles in rodents (21) and human subjects (4,9). Although other MAP kinase signaling cascades including ERK5 and ERK1/2 were obviously phosphorylated/activated in response to EPS-evoked contraction (Fig.…”

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise

“…2e,f,g). Phosphorylation of JNK could not be detected in white gastrocnemius muscle (data not shown), in line with the results from concentric non-damaging exercise [28]. In the liver, the phosphorylation signal of JNK was increased immediately after the treadmill run (Fig.…”

Acute elevation of circulating fatty acids impairs downstream insulin signalling in rat skeletal muscle in vivo independent of effects on stress signalling

“…In terms of JNK signalling, literature reports suggest that more severe physical insults such as atrophy or eccentric contraction of skeletal muscle result in robust phosphorylation of JNK (e.g. Boppart et al 1999, Carlson et al 2001, Martineau & Gardiner 2001, Hilder et al 2003. Our comparatively mild intervention of acute lipid infusion may not be sufficiently 'stressful' to lead to activation of such pathways and therefore JNK may not necessarily have a role in the initial stages of FA-induced impairments in insulin signalling.…”