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

Keith R. Laderoute, Keith A Webster

Research output: Contribution to journalArticle

156 Citations (Scopus)

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
Pages (from-to)336-344
Number of pages9
JournalCirculation Research
Volume80
Issue number3
StatePublished - Mar 8 1997

Fingerprint

Cardiac Myocytes
Oxidation-Reduction
Phosphotransferases
Anisomycin
Okadaic Acid
Myocardial Reperfusion
Genistein
Protein Kinase Inhibitors
Heat-Shock Proteins
Protein-Tyrosine Kinases
Protein Kinases
Muscle Cells
Reperfusion
Myocardial Ischemia
Glutathione
Transcription Factors
Necrosis
Ischemia
Cell Culture Techniques
Myocardial Infarction

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hypoxia/reoxygenation stimulates Jun kinase activity through redox signaling in cardiac myocytes. / Laderoute, Keith R.; Webster, Keith A.

In: Circulation Research, Vol. 80, No. 3, 08.03.1997, p. 336-344.

Research output: Contribution to journalArticle

Laderoute, Keith R. ; Webster, Keith A. / Hypoxia/reoxygenation stimulates Jun kinase activity through redox signaling in cardiac myocytes. In: Circulation Research. 1997 ; Vol. 80, No. 3. pp. 336-344.
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