Acute p38 MAPK activation decreases force development in ventricular myocytes

Yi Chen, Ravi Rajashree, Qinghang Liu, Polly Hofmann

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 NH 2 -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 αB-crystallin to the myofilaments. Using isolated cardiomyocytes, we determined that arsenite reduces isometric tension without a change in Ca 2+ sensitivity of tension via p38 MAPK and lowers myofibrillar actomyosin Mg 2+ -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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number6 54-6
StatePublished - Dec 1 2003

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p38 Mitogen-Activated Protein Kinases
Muscle Cells
Protein Phosphatase 2
Myofibrils
Adenosine Triphosphatases
Phosphorylation
HSP27 Heat-Shock Proteins
Actomyosin
Crystallins
Extracellular Signal-Regulated MAP Kinases
Protein Kinase Inhibitors
Cardiac Myocytes
Protein Kinases
arsenite
Phosphotransferases
Light

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Acute p38 MAPK activation decreases force development in ventricular myocytes. / Chen, Yi; Rajashree, Ravi; Liu, Qinghang; Hofmann, Polly.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 6 54-6, 01.12.2003.

Research output: Contribution to journalArticle

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