Acute p38 MAPK activation decreases force development in ventricular myocytes.
Evidence suggests that p38 mitogen-activated protein kinase (MAPK) activation influences cardiac function on an acute basis. The characterization and mechanisms by which this occurs were investigated in the present study. Adult rat ventricular myocytes treated with 1 mM arsenite for 30 min had a 16-fold increase in p38 MAPK phosphorylation that was attenuated by SB-203580 (a p38 MAPK inhibitor). Extracellular signal-regulated protein kinase (ERK) and c-Jun NH2-terminal kinase (JNK) were also minimally activated, but this activation was not sensitive to SB-203580. In addition, arsenite caused a p38 MAPK-independent translocation/activation of protein phosphatase 2a (PP2a) and decrease in phosphorylation of myosin light chain 2 (LC2). Arsenite-p38 MAPK activation led to translocation of heat shock protein 27 but not alpha B-crystallin to the myofilaments. Using isolated cardiomyocytes, we determined that arsenite reduces isometric tension without a change in Ca2+ sensitivity of tension via p38 MAPK and lowers myofibrillar actomyosin Mg2+-ATPase activity in a p38 MAPK-independent manner. Thus arsenite induces a p38 MAPK-independent change in PP2a and LC2 that may account for the arsenite-dependent decrease in ATPase and a p38 MAPK-dependent modification of the myofilaments that decreases myocardial force development.
Chen
Yi
Y
Department of Physiology, University of Tennessee Health Sciences Center, 894 Union Ave., Memphis, TN 38163, USA.
Rajashree
Ravi
R
Liu
Qinghang
Q
Hofmann
Polly
P
D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D024722:Cardiac Myosins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins; D006352:Heart Ventricles / Q000166:cytology; D006360:Heat-Shock Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology*; D018994:Myosin Light Chains / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D051381:Rats; D038203:alpha-Crystallin B Chain / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D018053:Arsenites; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D018994:Myosin Light Chains; D009363:Neoplasm Proteins; D038203:alpha-Crystallin B Chain; C107184:myosin light chain 2; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D024722:Cardiac Myosins; C015001:arsenite