Role of STAT3 in ischemic preconditioning

J Mol Cell Cardiol. 2001 Nov;33(11):1929-36. doi: 10.1006/jmcc.2001.1456.


We recently demonstrated that ischemic preconditioning (IPC) induced by cyclic episodes of short durations of ischemia and reperfusion potentiates a signal transduction cascade involving protein tyrosine kinases and MAP kinases. A rapid activation of janus kinase (JAK) and several signal transducers and activators of the transcription (STATs) including STAT3, STAT5A and STAT6 has been shown to occur during myocardial ischemia and reperfusion. This study sought to examine if JAK/STAT signaling pathway play any role in classical early phase of IPC. Isolated working rat hearts were perfused for 15 min with KHB buffer in the absence or presence of a JAK kinase inhibitor tyrphostin AG490 (5 microm) followed by IPC, 30 min global ischemia and 2 h of reperfusion. The results demonstrated extensive phosphorylation of JAK2 and STAT3 in the IPC hearts which was almost completely abolished by an inhibitor of JAK2, AG490. IPC displayed cardioprotection as evidenced by improved post-ischemic contractile recovery, decreased myocardial infarct size and reduced number of apoptotic cardiomyocytes. AG490 blocked IPC-mediated cardioprotection by altering the IPC-mediated survival signal into death signal. Thus, IPC-induced upregulation of antiapoptotic gene bcl-2 and downregulation of pro-apoptotic gene bax are decreased and increased, respectively, in the AG490 treated hearts. The results suggest that early phase of IPC potentiates JAK/STAT signaling by activating STAT3 which transmits a survival signal to the myocardium.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Survival
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Down-Regulation
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Heart / drug effects
  • Heart / physiology
  • In Situ Nick-End Labeling
  • Ischemic Preconditioning, Myocardial*
  • Myocardial Infarction / metabolism
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor
  • Signal Transduction
  • Time Factors
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Tyrphostins / pharmacology
  • Up-Regulation
  • bcl-2-Associated X Protein


  • Bax protein, rat
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Trans-Activators
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • bcl-2-Associated X Protein