Superoxide dismutase inhibits the expression of vascular cell adhesion molecule-1 and intracellular cell adhesion molecule-1 induced by tumor necrosis factor-alpha in human endothelial cells through the JNK/p38 pathways.
OBJECTIVE
Expression of adhesion molecules on endothelial cells and subsequent leukocyte recruitment are critical early events in the development of atherosclerosis. We tried to study possible effects of Cu/Zn superoxide dismutase (SOD) on adhesion molecule expression and its underlying mechanism in the prevention and treatment of cardiovascular disorders.


RESULTS
Human aortic endothelial cells (HAECs) were transfected with adenovirus carrying the human SOD gene (AdSOD) to investigate whether SOD expression in HAECs attenuated tumor necrosis factor (TNF)-alpha-induced reactive oxygen species production and adhesion molecule expression and to define the mechanisms involved. SOD expression significantly suppressed TNF-alpha-induced expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and reduced the binding of the human neutrophils to TNF-alpha-stimulated HAECs. SOD expression suppressed c-JUN N-terminal kinase and p38 phosphorylation. It also attenuated intracellular superoxide anion production and NADPH oxidase activity in TNF-alpha-treated HAECs.


CONCLUSIONS
These results provide evidence that SOD expression in endothelial cells attenuates TNF-alpha-induced superoxide anion production and adhesion molecule expression, and that this protective effect is mediated by decreased JNK and p38 phosphorylation and activator protein-1 and nuclear factor kappaB inactivation. These results suggest that SOD has antiinflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory response. Superoxide dismutase overexpression in endothelial cells attenuates tumor necrosis factor alpha-induced superoxide anion production and adhesion molecule expression, and this effect is mediated by decreased JNK and p38 phosphorylation and AP-1 and nuclear factor B inactivation. These results suggest that superoxide dismutase may play an important role in the prevention of atherosclerosis and inflammatory response.
Lin
Shing-Jong
SJ
Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University, Taiwan, Republic of China.
Shyue
Song-Kun
SK
Hung
Ya-Yun
YY
Chen
Yung-Hsiang
YH
Ku
Hung-Hai
HH
Chen
Jaw-Wen
JW
Tam
Ka-Bik
KB
Chen
Yuh-Lien
YL
D000873:Anthracenes / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003864:Depression, Chemical; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000166:cytology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D016328:NF-kappa B; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C000606290:SOD1 protein, human; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; C432165:pyrazolanthrone; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one