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

Journal Article (Journal Article)

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 p38alpha (p38alphadn) or p38beta (p38betadn). Hearts were subjected to 20 min ischemia and 40 min reperfusion. Immunofluorescence staining for p38alphadn and p38betadn protein was performed on neonatal cardiomyocytes infected with adenovirus expressing flag-tagged p38alphadn and p38betadn protein. Basal contractile function was increased in both p38alphadn and p38betadn hearts compared to WT. Ischemic injury was increased in p38betadn vs. WT hearts, as indicated by lower posti-schemic recoveries of contractile function and ATP. However, despite a similar increase in contractility, ischemic injury was not increased in p38alphadn vs. WT hearts. Immunohistological analysis of cardiomyocytes with comparable levels of protein overexpression show that p38alphadn and p38betadn proteins were co-localized with sarcomeric alpha-actinin, however, p38alphadn was detected in the nucleus while p38betadn 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.

Full Text

Duke Authors

Cited Authors

  • Cross, HR; Li, M; Petrich, BG; Murphy, E; Wang, Y; Steenbergen, C

Published Date

  • September 2009

Published In

Volume / Issue

  • 96 / 3

Start / End Page

  • 307 - 323

PubMed ID

  • 19706373

Pubmed Central ID

  • PMC3137881

International Standard Serial Number (ISSN)

  • 0231-424X

Digital Object Identifier (DOI)

  • 10.1556/APhysiol.96.2009.3.5

Language

  • eng

Conference Location

  • Hungary