Effect of p38 MAP kinases on contractility and ischemic injury in intact heart

H. R. Cross, M. Li, B. G. Petrich, E. Murphy, Y. Wang, Ch Steenbergen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The p38 MAP kinases are stress-activated MAP kinases whose induction is often associated with the onset of heart failure. This study investigated the role of p38 MAP kinase isoforms in the regulation of myocardial contractility and ischemia/reperfusion injury using mice with cardiac-specific expression of kinase dead (dominant negative) mutants of p38α (p38αdn) or p38β (p38βdn). Hearts were subjected to 20 min ischemia and 40 min reperfusion. Immunofluorescence staining for p38αdn and p38βdn protein was performed on neonatal cardiomyocytes infected with adenovirus expressing flag-tagged p38αdn and p38βdn protein. Basal contractile function was increased in both p38αdn and p38βdn hearts compared to WT. Ischemic injury was increased in p38βdn vs. WT hearts, as indicated by lower postischemic recoveries of contractile function and ATP. However, despite a similar increase in contractility, ischemic injury was not increased in p38βdn vs. WT hearts. Immunohistological analysis of cardiomyocytes with comparable levels of protein overexpression show that p38αdn and p38βdn proteins were co-localized with sarcomeric α-actinin, however, p38αdn was detected in the nucleus while p38βdn was exclusively detected in the cytosol. In summary, attenuated p38 activity led to increased myocardial contractility; specific isoforms of p38 and their sub-cellular localization may have different roles in modulating ischemic injury.

Original languageEnglish (US)
Pages (from-to)307-323
Number of pages17
JournalActa physiologica Hungarica
Issue number3
StatePublished - 2009


  • Contractile function
  • Energetics
  • Ischemia
  • NMR spectroscopy
  • P38 MAP kinase

ASJC Scopus subject areas

  • Physiology (medical)


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