To study the in vivo dynamics of hypoxia-inducible factor 1α (HIF-1α), master regulator of O2-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% O2), 23-hr hypoxia, and 23-hr hypoxia, followed by reoxygenation. HIF-1a 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 NH2-terminal kinases (JNKs), measured as phosphorylated c-Jun, increased 3-fold after 1-hr hypoxia and remained sustained afterward. Furthermore, HIF-1α 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-1α is overexpressed in vivo in the hypoxic myocardium, and its acute induction by hypoxia is correlated with that of p38. Copyright
Heart HIF-1α and MAP kinases during hypoxia: are they associated in vivo? / A. Caretti, S. Morel, G. Milano, M. Fantacci, P. Bianciardi, R. Ronchi, G. Vassalli, L.K. von Segesser, M. Samaja. - In: EXPERIMENTAL BIOLOGY AND MEDICINE. - ISSN 1535-3702. - 232:7(2007), pp. 887-894.
|Titolo:||Heart HIF-1α and MAP kinases during hypoxia: are they associated in vivo?|
|Parole Chiave:||c-Jun; ERK1/2; HSP27; JNK; p38; SB202190|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||2007|
|Appare nelle tipologie:||01 - Articolo su periodico|