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

Eccentric contractions require the lengthening of skeletal muscle during fo rce production and result in acute and prolonged muscle injury. Because a v ariety of stressors, including physical exercise and injury, can result in the activation of the c-Jun NH2-terminal kinase (JNK) intracellular signali ng cascade in skeletal muscle, we investigated the effects of eccentric exe rcise on the activation of this stress-activated protein kinase in human sk eletal muscle. Twelve healthy subjects (7 men, 5 women) completed maximal c oncentric or eccentric knee extensions on a KinCom isokinetic dynamometer ( 10 sets, 10 repetitions). Percutaneous needle biopsies were obtained from t he vastus lateralis muscle 24 h before exercise (basal), immediately postex ercise, and 6 h postexercise. Whereas both forms of exercise increased JNK activity immediately postexercise, eccentric contractions resulted in a muc h 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 imme diate upstream regulator of JNK, was similarly activated by concentric and eccentric exercise. Because the activation of JNK promotes the phosphorylat ion of a variety of transcription factors, including c-Jun, the results fro m this study suggest that JNK may be involved in the molecular and cellular adaptations that occur in response to injury-producing exercise in human s keletal muscle.