Distinct roles of p42/p44ERK and p38 MAPK in oxidant-induced AP-1 activation and cardiomyocyte hypertrophy

Victoria C. Tu, Joe J. Bahl, Qin M. Chen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Cardiac hypertrophy is an adaptive response to a number of heart diseases including myocardial infarction. Although it can be compensatory at first, sustained hypertrophy is often a transition to heart failure. We have found that cardiomyocytes in culture can survive mild doses of H2O2 but develop hypertrophy involving activation of p70 S6 kinase 1 (p70S6K1). Here, the role of p42/p44ERK and p38 MAPK in oxidant-induced hypertrophy is tested. H2O2-induced phosphorylation (activation) of p42/p44ERK and p38 within 10 min of 200 μM H2O 2 exposure. Although p42/p44ERK remained highly phosphorylated from 60 to 120 min, the level of p38 phosphorylation reached highest at 60 min and started to decline at 90 min. Inhibiting ERKs with PD98059 attenuated H2O2-induced AP-1 activation but did not affect H2O2-induced p70S6K1 activation or cardiomyocyte en largement as measured by increases in cell volume and protein content. In contrast, the p38 inhibitor SB202190 has no inhibitory effect on AP-1 activation but partially prevented H2O2 from inducing p70S6K1 activation and cell enlargement. These data suggest that while p42/p44 ERK participates in gene expression associated with hypertrophy, p38 may regulate cell size increase by p70S6K1 activation.

Original languageEnglish (US)
Pages (from-to)119-133
Number of pages15
JournalCardiovascular toxicology
Issue number2
StatePublished - 2003


  • Cell size
  • Gene expression
  • MAPKs
  • Oxidativestress
  • Pharmacologic inhibitors
  • Phosphoinositide3-kinase
  • Phosphorylation
  • p70S6 kinase-1

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine


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