Eccentric exercise markedly increases c-Jun NH(2)-terminal kinase activity in human skeletal muscle.
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.
Boppart
M D
MD
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Massachusetts 02111, USA.
Aronson
D
D
Gibson
L
L
Roubenoff
R
R
Abad
L W
LW
Bean
J
J
Goodyear
L J
LJ
Fielding
R A
RA
D000328:Adult; D015153:Blotting, Western; D003402:Creatine Kinase / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D003402:Creatine Kinase