Phosphorylation of glycogen synthase kinase-3β during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective

Haiyan Tong, Kenichi Imahashi, Charles Steenbergen, Elizabeth Murphy

Research output: Contribution to journalArticle

Abstract

We previously reported that activation of phosphatidylinositol-3-kinase (PI3-kinase) is involved in ischemic preconditioning (PC). Our goal was to determine downstream targets of PI3-kinase. In perfused rat hearts, PC (4 cycles of 5 minutes of ischemia and 5 minutes of reflow) increased phosphorylation of glycogen synthase kinase-3β (GSK-3β), a downstream target of PI3-kinase and protein kinase B (PKB), an effect that was blocked by wortmannin. Because phosphorylation inactivates GSK-3β, we examined whether PC-induced phosphorylation and inhibition of GSK-3β is important in PC by using two inhibitors of GSK-3β, lithium and SB 216763. Pretreatment of perfused rat hearts with lithium or SB 216763, before ischemia, mimicked the protective effects of PC; hearts treated with either lithium or SB 216763 had improved postischemic function and reduced infarct size. These findings indicate that inhibition of GSK-3β is protective and that this PI3-kinase-dependent signaling pathway may play an important role in ischemic preconditioning.

Original languageEnglish (US)
Pages (from-to)377-379
Number of pages3
JournalCirculation research
Volume90
Issue number4
DOIs
StatePublished - Mar 8 2002

Keywords

  • Glycogen synthase kinase-3/β
  • Ischemic preconditioning
  • Phosphatidylinositol-3-kinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Phosphorylation of glycogen synthase kinase-3β during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective'. Together they form a unique fingerprint.

  • Cite this