Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death

Biochem Biophys Res Commun. 2005 Jul 29;333(2):562-7. doi: 10.1016/j.bbrc.2005.05.151.

Abstract

The molecular basis of myocardial cell death in the ischemia-reperfused heart still remains to be clarified. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We studied ASK1(-/-) mice to examine the role of ASK1 in ischemia-reperfusion injury. In the wild-type heart, ischemia-reperfusion resulted in necrotic injury, whereas infarct size was drastically reduced in the ASK1(-/-) heart. The necrotic injury was not accompanied with any evidence of apoptosis such as an increase in TUNEL-positive cells, DNA fragmentation or the activation of caspase-3. ASK1(-/-) cardiomyocytes were more resistant to H(2)O(2)- or Ca(2+)-induced apoptotic and non-apoptotic cell death compared with wild-type cells. These data suggest that ASK1 is involved in necrosis as well as apoptosis and that ASK1-dependent necrosis is likely to contribute to myocardial cell death in the ischemia-reperfused heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cells, Cultured
  • MAP Kinase Kinase Kinase 5 / deficiency
  • MAP Kinase Kinase Kinase 5 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / enzymology*
  • Myocytes, Cardiac / pathology*
  • Necrosis*
  • Reperfusion Injury / enzymology*
  • Reperfusion Injury / pathology*

Substances

  • MAP Kinase Kinase Kinase 5