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Am J Physiol Cell Physiol 275: C555-C561, 1998;
0363-6143/98 $5.00
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Vol. 275, Issue 2, C555-C561, August 1998

Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle

Doron Aronson1, Jørgen F. P. Wojtaszewski2, Anders Thorell3, Jonas Nygren3, David Zangen1, Erik A. Richter2, Olle Ljungqvist3, Roger A. Fielding4, and Laurie J. Goodyear1

1 Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and 4 Department of Health Sciences, Sargent College of Allied Health Professions, Boston University, Boston, Massachusetts 02215; 2 Copenhagen Muscle Research Center, August Krogh Institute, University of Copenhagen, DK-2100 Copenhagen, Denmark; and 3 Department of Surgery, Karolinska Hospital and Institute, S-10401 Stockholm, Sweden

The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. However, it is not known whether these signaling cascades also participate in the response to injury in human tissues. To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing.

mitogen-activated protein kinase; signal transduction; stress enzymology


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