TY - JOUR
T1 - NF-κB is activated and ICAM-1 gene expression is upregulated during reoxygenation of human brain endothelial cells
AU - Howard, Eugene F.
AU - Chen, Qiang
AU - Cheng, Charles
AU - Carroll, James E.
AU - Hess, David
N1 - Funding Information:
This study was supported by the American Heart Association, the Veterans Affairs Medical Research Service and a Biomedical Research Support Grant from the Medical College of Georgia. The authors wish to acknowledge the assistance of Dr. Yeini Thompson, Julie Folk and Ashley Stone.
PY - 1998/6/5
Y1 - 1998/6/5
N2 - Reperfusion injury is mediated, in part, by the upregulated expression of genes in microvascular endothelial cells that encode for inflammatory cytokines and adhesion molecules. The redox-regulated transcription factor, nuclear factor kappa B (NF-κB), may play a major role in the induced expression of these genes in this study we use cultured human brain microvascular endothelial cells (HBMEC) to investigate whether reoxygenation of hypoxic HBMEC results in the activation of NF-κB and the upregulation of the adhesion molecule, ICAM-1. When HBMEC were subjected to hypoxia followed by reoxygenation but not hypoxia alone, an NF-κB complex composed of p65 and p50 Rel proteins was rapidly activated within 15-30 min. Four hours later, expression of the ICAM-1 gene was significantly upregulated. The antioxidant pyrrolidine dithiocarbamate and the proteasome inhibitor, n-Tosyl-Phe- chloromethyl ketone, blocked both the activation of NF-κB and the upregulation of the ICAM-1 gene. These results indicate that NF-κB is activated in HBMEC by reoxygenation and may play a significant role in the upregulation of the ICAM-1 gene. Agents which inhibit NF-κB activation may be potential therapeutic agents in acute ischemic stroke.
AB - Reperfusion injury is mediated, in part, by the upregulated expression of genes in microvascular endothelial cells that encode for inflammatory cytokines and adhesion molecules. The redox-regulated transcription factor, nuclear factor kappa B (NF-κB), may play a major role in the induced expression of these genes in this study we use cultured human brain microvascular endothelial cells (HBMEC) to investigate whether reoxygenation of hypoxic HBMEC results in the activation of NF-κB and the upregulation of the adhesion molecule, ICAM-1. When HBMEC were subjected to hypoxia followed by reoxygenation but not hypoxia alone, an NF-κB complex composed of p65 and p50 Rel proteins was rapidly activated within 15-30 min. Four hours later, expression of the ICAM-1 gene was significantly upregulated. The antioxidant pyrrolidine dithiocarbamate and the proteasome inhibitor, n-Tosyl-Phe- chloromethyl ketone, blocked both the activation of NF-κB and the upregulation of the ICAM-1 gene. These results indicate that NF-κB is activated in HBMEC by reoxygenation and may play a significant role in the upregulation of the ICAM-1 gene. Agents which inhibit NF-κB activation may be potential therapeutic agents in acute ischemic stroke.
KW - Human brain microvascular endothelial cells
KW - Hypoxia-reoxygenation
KW - ICAM- 1
KW - Ischemic stroke
KW - Nuclear factor kappa B
KW - Reperfusion injury
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U2 - 10.1016/S0304-3940(98)00239-0
DO - 10.1016/S0304-3940(98)00239-0
M3 - Article
C2 - 9654343
AN - SCOPUS:0032486242
SN - 0304-3940
VL - 248
SP - 199
EP - 203
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -