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 language | English |
|---|---|
| Pages (from-to) | 336-344 |
| Number of pages | 9 |
| Journal | Circulation Research |
| Volume | 80 |
| Issue number | 3 |
| State | Published - Mar 8 1997 |
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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 journal › Article
}
TY - JOUR
T1 - Hypoxia/reoxygenation stimulates Jun kinase activity through redox signaling in cardiac myocytes
AU - Laderoute, Keith R.
AU - Webster, Keith A
PY - 1997/3/8
Y1 - 1997/3/8
N2 - 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.
AB - 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.
KW - antioxidant
KW - glutathione
KW - ischemia/reperfusion
KW - mitogen-activated protein kinase
KW - stress-activated protein kinase
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UR - http://www.scopus.com/inward/citedby.url?scp=0031057890&partnerID=8YFLogxK
M3 - Article
C2 - 9048653
AN - SCOPUS:0031057890
VL - 80
SP - 336
EP - 344
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 3
ER -