TY - JOUR
T1 - HIF-1α reveals a binding activity to the promoter of iNOS gene after permanent middle cerebral artery occlusion
AU - Matrone, C.
AU - Pignataro, G.
AU - Molinaro, P.
AU - Irace, C.
AU - Scorziello, A.
AU - Di Renzo, G. F.
AU - Annunziato, Lucio
PY - 2004/7
Y1 - 2004/7
N2 - Hypoxia inducible factor (HIF-1)-1α is a specific, oxygen-sensitive protein that regulates the activity of HIF-1, a transcriptional factor that increases after cerebral ischemia and may either promote or prevent neuronal survival. In this study to determine whether the inducible nitric oxide synthase (iNOS) gene containing the sequence of the hypoxia-responsive enhancer (HRE) was an HIF-1 target after cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAO), electrophoretic mobility shift assay (EMSA) and iNOS western blot analysis were performed in the ischemic core, in the area surrounding the infarct and in the hippocampus ipsilateral and contralateral to the lesion. In addition, both HIF-1α mRNA and protein expression were examined in the ischemic core, in the area surrounding the ischemic core and in the hippocampus ipsilateral to the insult. Our results revealed that pMCAO up-regulates iNOS protein in the ischemic core, in the area surrounding the ischemic core and in the hippocampus ipsilateral to the lesion, and that the activation of iNOS expression is mediated by HIF-1. Moreover, HIF-1α mRNA and protein levels increased in the ischemic core and in the hippocampus ipsilateral to the lesion compared with the levels obtained in the corresponding areas of sham-operated controls or in the contralateral hemisphere. Particularly in the area surrounding the ischemic core, HIF-1α protein accumulated during pMCAO although mRNA did not increase. Our study suggests that the activation of HIF-1 might be involved in the mechanisms whereby iNOS promotes cell survival and/or death after cerebral ischemia.
AB - Hypoxia inducible factor (HIF-1)-1α is a specific, oxygen-sensitive protein that regulates the activity of HIF-1, a transcriptional factor that increases after cerebral ischemia and may either promote or prevent neuronal survival. In this study to determine whether the inducible nitric oxide synthase (iNOS) gene containing the sequence of the hypoxia-responsive enhancer (HRE) was an HIF-1 target after cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAO), electrophoretic mobility shift assay (EMSA) and iNOS western blot analysis were performed in the ischemic core, in the area surrounding the infarct and in the hippocampus ipsilateral and contralateral to the lesion. In addition, both HIF-1α mRNA and protein expression were examined in the ischemic core, in the area surrounding the ischemic core and in the hippocampus ipsilateral to the insult. Our results revealed that pMCAO up-regulates iNOS protein in the ischemic core, in the area surrounding the ischemic core and in the hippocampus ipsilateral to the lesion, and that the activation of iNOS expression is mediated by HIF-1. Moreover, HIF-1α mRNA and protein levels increased in the ischemic core and in the hippocampus ipsilateral to the lesion compared with the levels obtained in the corresponding areas of sham-operated controls or in the contralateral hemisphere. Particularly in the area surrounding the ischemic core, HIF-1α protein accumulated during pMCAO although mRNA did not increase. Our study suggests that the activation of HIF-1 might be involved in the mechanisms whereby iNOS promotes cell survival and/or death after cerebral ischemia.
KW - Hippocampus
KW - Hypoxia inducible factor-1
KW - Inducible nitric oxide synthase
KW - Inducible nitric oxide synthase promoter
KW - Ischemia
KW - pMCAO
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U2 - 10.1111/j.1471-4159.2004.02483.x
DO - 10.1111/j.1471-4159.2004.02483.x
M3 - Article
C2 - 15228594
AN - SCOPUS:3142746742
VL - 90
SP - 368
EP - 378
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -