Oxygen radicals trigger activation of NF-κB and AP-1 and upregulation of ICAM-1 in reperfused canine heart

Haiying Fan, Baogui Sun, Qiuping Gu, Anne Lafond-Walker, Suyi Cao, Lewis Becker

Research output: Contribution to journalArticle

Abstract

We investigated whether oxygen radicals generated during ischemia-reperfusion trigger postischemic inflammation in the heart. Closed-chest dogs underwent 90-min coronary artery occlusion, followed by 1- or 3-h reperfusion: 10 dogs received the cell-permeant oxygen radical scavenger N-(2-mercaptopropionyl)-glycine (MPG; 8 mg·kg-1·h-1 intracoronary) beginning 5 min before reperfusion, and 9 dogs received vehicle. Blood flow (microspheres), intercellular adhesion molecule (ICAM)-I protein expression (immunohistochemistry), ICAM-1 gene activation (Northern blotting), nuclear DNA binding activity of nuclear factor (NF)-κB and AP-1 (electrophoretic mobility shift assays), and neutrophil (PMN) accumulation (myeloperoxidase activity) were assessed in myocardial tissue samples. ICAM-1 protein expression was high in vascular endothelium after ischemia-reperfusion but was markedly reduced by MPG. MPG treatment also markedly decreased expression of ICAM-1 mRNA and tissue PMN accumulation. Nuclear DNA binding activities of NF-κB and AP-1, increased by ischemia-reperfusion, were both markedly decreased by MPG at 1 h of reperfusion. However, by 3 h, AP-1 activity was only modestly reduced by MPG and NF-κB activity was not significantly different from ischemic-reperfused controls. These results suggest that oxygen radicals generated in vivo during reperfusion trigger early activation of NF-κB and AP-1, resulting in upregulation of the ICAM-1 gene in vascular endothelium and subsequent tissue accumulation of activated PMNs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number5 51-5
StatePublished - 2002

Fingerprint

Transcription Factor AP-1
Intercellular Adhesion Molecule-1
Reperfusion
Canidae
Reactive Oxygen Species
Up-Regulation
Ischemia
Vascular Endothelium
Dogs
Coronary Occlusion
DNA
Cell Adhesion Molecules
Electrophoretic Mobility Shift Assay
Microspheres
Northern Blotting
Glycine
Transcriptional Activation
Peroxidase
Coronary Vessels
Proteins

Keywords

  • Neutrophils
  • Oxidative stress
  • Reperfusion injury
  • Vascular endothelium

ASJC Scopus subject areas

  • Physiology

Cite this

Oxygen radicals trigger activation of NF-κB and AP-1 and upregulation of ICAM-1 in reperfused canine heart. / Fan, Haiying; Sun, Baogui; Gu, Qiuping; Lafond-Walker, Anne; Cao, Suyi; Becker, Lewis.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 282, No. 5 51-5, 2002.

Research output: Contribution to journalArticle

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AU - Cao, Suyi

AU - Becker, Lewis

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