Inhibition of NF-kappaB Activation Increases Oxygen-Glucose Deprivation-Induced Cerebral Endothelial Cell Death.
- Author:
Jinu LEE
1
;
Chul Hoon KIM
;
Kyu Dae SHIM
;
Young Soo AHN
Author Information
1. Brain Korea 21 Project for Medical Sciences, Brain Research Institute, Yonsei University College of Medicine, Seoul 120 752, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Cerebral endothelial cell;
Oxygen-glucose deprivation;
Cell death;
Nuclear factor kappa B
- MeSH:
Animals;
Aspirin;
Brain;
Brain Ischemia;
Cell Death;
Cell Line;
Endothelial Cells*;
Mice;
NF-kappa B*;
Reperfusion;
Reperfusion Injury;
Stroke;
Zinc
- From:The Korean Journal of Physiology and Pharmacology
2003;7(2):65-72
- CountryRepublic of Korea
- Language:English
-
Abstract:
Increasing evidences suggest that ischemia-induced vascular damage is an integral step in the cascade of the cellular and 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-kappaB) activation during ischemic injury was investigated. OGD was found to activate NF-kappaB and to induce bEnd.3 cell death in a time-dependent manner. OGD phosphorylated neither 32 Ser nor 42 Tyr of IkappaBalpha. OGD did not change the amount of IkappaB alpha. 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 ischemic insult in cerebral endothelial cells. Three known as NF-kappaB inhibitors, including pyrrolidine dithiocarbamate (PDTC) plus zinc, aspirin and caffeic acid phenethyl ester (CAPE), inhibited OGD-induced NF-kappaB 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-kappaB activity. These results suggest that NF-kappaB activation might be a protective mechanism for OGD-induced cell death in bEnd.3.
