Article: article from journal or magazin.
Heart HIF-1alpha and MAP kinases during hypoxia: are they associated in vivo?
Experimental Biology And Medicine
Publication types: Journal Article
To study the in vivo dynamics of hypoxia-inducible factor 1alpha (HIF-1alpha), master regulator of O(2)-dependent gene expression, and mitogen-activated protein kinases (MAPKs) in the hypoxic myocardium, Sprague-Dawley rats (n = 4 to 6 per group) were exposed to 1-hr hypoxia (10% O(2)), 23-hr hypoxia, and 23-hr hypoxia, followed by reoxygenation. HIF-1alpha increased 15-fold after 1-hr hypoxia, remained constant for 23 hrs, and returned to baseline on reoxygenation. Extracellular signal-regulated kinases (ERK1/2) were unchanged throughout. Phosphorylated p38 increased 4-fold after 1-hr hypoxia and returned to baseline within 23-hr hypoxia. The activity of stress-activated protein kinases/c-Jun NH(2)-terminal kinases (JNKs), measured as phosphorylated c-Jun, increased 3-fold after 1-hr hypoxia and remained sustained afterward. Furthermore, HIF-1alpha was halved in rats that were administered with the p38 inhibitor SB202190 and made hypoxic for 1 hr. In conclusion, although very sensitive to the reoxygenation, HIF-1alpha is overexpressed in vivo in the hypoxic myocardium, and its acute induction by hypoxia is correlated with that of p38.
Animals, Anoxia, Cytosol/metabolism, Gene Expression Regulation, Enzymologic, Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis, Imidazoles/pharmacology, MAP Kinase Signaling System, Male, Myocardium/metabolism, Oxygen/metabolism, Phosphorylation, Pyridines/pharmacology, Rats, Rats, Sprague-Dawley, Time Factors, p38 Mitogen-Activated Protein Kinases/biosynthesis
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