Effects of concentric and eccentric contractions on phosphorylation of MAPK (erk1/2) and MAPK(38) in isolated rat skeletal muscle

1. Exercise and contractions of isolated skeletal muscle induce phosphoryla tion 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 stretche s were used to discriminate between effects of metabolic/ionic and mechanic al alterations on phosphorylation of two MAPKs: extracellular signal-regula ted kinase 1 and 2 (MAPK(erk1/2)) and stress-activated protein kinase p38 ( MAPK(p38)). 3. Concentric contractions induced a 5-fold increase in MAPK(erk1/2) phosph orylation. Application of the antioxidants N-acetylcysteine (20 mM) or dith iothreitol (5 mM) suppressed concentric contraction-induced increase in MAP K(erk1/2) phosphorylation. Mild passive stretches of the muscle increased M APK(erk1/2) phosphorylation by 1.8-fold, whereas the combination of acidosi s and passive stretches resulted in a 2.8-fold increase. Neither concentric contractions, nor mild stretches nor acidosis significantly affected phosp horylation of MAPK(p38). 4. High force applied upon muscle by means of either eccentric contractions or severe passive stretchers resulted in 5.7- and 9.5-fold increases of ph osphorylated MAPK(erk1/2), respectively, whereas phosphorylation of MAPK(p3 8) increased by 7.6- and 1.9-fold (not significant), respectively. 5. We conclude that in isolated rat skeletal muscle an increase in phosphor ylation of both MAPK(erk1/2) and MAPK(p38) is induced by mechanical alterat ions, whereas contraction-related metabolic/ionic changes (reactive oxygen species and acidosis) cause increased phosphorylation MAPK(erk1/2) only. Th us, contraction-induced phosphorylation can he explained by the combined ac tion of increased production of reactive oxygen species, acidification and mechanical perturbations for MAPK(erk1/2) and by high mechanical stress for MAPK(p38).