EXERCISE STIMULATES C-JUN NH2 KINASE-ACTIVITY AND C-JUN TRANSCRIPTIONAL ACTIVITY IN HUMAN SKELETAL-MUSCLE

Exercise causes selective changes in gene expression leading to altera tions in the structure and function of human skeletal muscle. However, little is known about the specific signaling pathways that enable exe rcise to modulate gene regulatory events. We determined the effects of exercise on c-Jun NH2-terminal kinase (JNK) activity, a signaling mol ecule involved in the regulation of transcription. Biopsies of vastus lateralis muscle were taken from eight subjects at rest and after 60 m in of cycle ergometer exercise. Exercise increased JNK activity in all subjects (5.9 +/- 1.8 fold above basal). JNK activation was associate d with an increased expression of its downstream nuclear target c-Jun mRNA. When two additional subjects were studied using a one-legged exe rcise protocol, JNK activity increased only in the exercising leg, ind icating that exercise-induced JNK signaling represents an intrinsic re sponse of the contracting muscle, rather than a systemic response to e xercise. These studies demonstrate that the JNK pathway may serve as a link between contractile activity and transcriptional responses in hu man skeletal muscle. (C) 1998 Academic Press.