The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Inhibition of $NF-{\kappa}B$ Activation Increases Oxygen-Glucose Deprivation-Induced Cerebral Endothelial Cell Death

  • Lee, Jin-U (Brain Korea 21 Project for Medical Sciences, Brain Research Institute and Department of Pharmacology, Yonsei University College of Medicine) ;
  • Kim, Chul-Hoon (Brain Korea 21 Project for Medical Sciences, Brain Research Institute and Department of Pharmacology, Yonsei University College of Medicine) ;
  • Shim, Kyu-Dae (Department of Anaesthesiology, Youngdong Severance Hospital, Yonsei University College of Medicine) ;
  • Ahn, Young-Soo (Brain Korea 21 Project for Medical Sciences, Brain Research Institute and Department of Pharmacology, Yonsei University College of Medicine)
  • Published : 2003.04.21
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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-${\kappa}B$) activation during ischemic injury was investigated. OGD was found to activate NF-${\kappa}B$ and to induce bEnd.3 cell death in a time-dependent manner. OGD phosphorylated neither 32 Ser nor 42 Tyr of $I{\kappa}B{\alpha}$. OGD did not change the amount of $I{\kappa}B{\alpha}$. 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-${\kappa}B$ inhibitors, including pyrrolidine dithiocarbamate (PDTC) plus zinc, aspirin and caffeic acid phenethyl ester (CAPE), inhibited OGD-induced NF-${\kappa}B$ 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-${\kappa}B$ activity. These results suggest that NF-${\kappa}B$ activation might be a protective mechanism for OGD-induced cell death in bEnd.3.

Keywords

References

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