Inhibition of NF-κB Activation Increased Oxygen-Glucose Deprivation-Induced Cerebral Endothelial Cell Death

Abstract

INcreasing evidences suggest that ischemia-induced vascular damage in an integral step in the cascade of the cellular abd molecular events initiated by cerebral ischemia. In the present study, employing a mouse brain endothelioma-derived cell line, bEnd.3, and oxygen-glucose deprivation (OGD) as an in vitro stroke model, the role of nuclear factor kappa B(NF-κB) activation during ischemic injury was investigated. OGD was found to activate NF-κB and to induce bEnd.3 cell death in a time-dependent manner. OGD phosphorylated neither 32 Ser nor 42 Tyr of IκBα. OGD did not chage the amount of IκBα. The extents of OGD-induced cell death after 8 h, 10 h, 12 h and 14 h of OGD were 10%, 35%, 60% and 85%, respectively. Reperfusion following OGD did not cause additional cell death, indicating no reperfusion injury after ischemia insult in cerebral endothelial cells. There known as NF-κB inhibitors, including pyrrolidine dithiocarbamate (PDTC) plus zinc, aspirin and caffeic acid phenethyl ester (CAPE), inhibited OGD-induced NF-κB activation and increased OGD-induced bEnd.3 cell death in a dose dependent manner. there were no changes in the protein levels of bcl-2, bax and p53 which are modulated by NF-κB activity. these results suggest that NF-κB activation might be a protective mechanism for OGD-induced cell death in bEnd.3.