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J Physiol Volume 535, Number 1, 155-164, August 15, 2001
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Journal of Physiology (2001), 535.1, pp. 155-164
© Copyright 2001 The Physiological Society

Effects of concentric and eccentric contractions on phosphorylation of MAPKerk1/2 and MAPKp38 in isolated rat skeletal muscle


Charlott Wretman, Arimantas Lionikas, Ulrika Widegren, Jan Lännergren, Håkan Westerblad and Jan Henriksson


Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden

  1. Exercise and contractions of isolated skeletal muscle induce phosphorylation of mitogen-activated protein kinases (MAPKs) by undefined mechanisms. The aim of the present study was to determine exercise-related triggering factors for the increased phosphorylation of MAPKs in isolated rat extensor digitorum longus (EDL) muscle.
  2. Concentric or eccentric contractions, or mild or severe passive stretches were used to discriminate between effects of metabolic/ionic and mechanical alterations on phosphorylation of two MAPKs: extracellular signal-regulated kinase 1 and 2 (MAPKerk1/2) and stress-activated protein kinase p38 (MAPKp38).
  3. Concentric contractions induced a 5-fold increase in MAPKerk1/2 phosphorylation. Application of the antioxidants N-acetylcysteine (20 mM) or dithiothreitol (5 mM) suppressed concentric contraction-induced increase in MAPKerk1/2 phosphorylation. Mild passive stretches of the muscle increased MAPKerk1/2 phosphorylation by 1.8-fold, whereas the combination of acidosis and passive stretches resulted in a 2.8-fold increase. Neither concentric contractions, nor mild stretches nor acidosis significantly affected phosphorylation of MAPKp38.
  4. High force applied upon muscle by means of either eccentric contractions or severe passive stretches resulted in 5.7- and 9.5-fold increases of phosphorylated MAPKerk1/2, respectively, whereas phosphorylation of MAPKp38 increased by 7.6- and 1.9-fold (not significant), respectively.
  5. We conclude that in isolated rat skeletal muscle an increase in phosphorylation of both MAPKerk1/2 and MAPKp38 is induced by mechanical alterations, whereas contraction-related metabolic/ionic changes (reactive oxygen species and acidosis) cause increased phosphorylation of MAPKerk1/2 only. Thus, contraction-induced phosphorylation can be explained by the combined action of increased production of reactive oxygen species, acidification and mechanical perturbations for MAPKerk1/2 and by high mechanical stress for MAPKp38.



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