Hypoxia/reoxygenation stimulates Jun kinase activity through redox signaling in cardiac myocytes

Keith R. Laderoute, Keith A. Webster

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

Hypoxia and reoxygenation are principal components of myocardial ischemia and reperfusion and have distinctive effects on the tissue. Both conditions have been associated with inflammation, necrosis, apoptosis, and myocardial infarction. Using a cell culture model of ischemia and reperfusion in which cardiac myocytes were exposed to cycles of hypoxia and reoxygenation, we report here thai reoxygenation, but not hypoxia alone, caused sustained ≃10-fold increases in phosphorylation of the amino-terminal domain of the c-jun transcription factor. The activation was similar to treatments with anisomycin or okadaic acid and correlated with the hypoxia mediated depression of intracellular glutathione. Reoxygenation-induced c- Jun kinase activity was reduced by preincubating myocytes during the hypoxia phase with the spin-trap agent α-phenyl N-tert-butylnitrone or with N- acelylcysteine. The kinase activation was also inhibited by the tyrosine kinase inhibitor genistein but not by other protein kinase inhibitors. These results implicate unquenched reactive oxygen intermediates as the stimulus that initiates a kinase pathway involving the stress-activated protein kinases (JNKs/SAPKs) in reoxygenated cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)336-344
Number of pages9
JournalCirculation research
Volume80
Issue number3
DOIs
StatePublished - Jan 1 1997

Keywords

  • antioxidant
  • glutathione
  • ischemia/reperfusion
  • mitogen-activated protein kinase
  • stress-activated protein kinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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