Overexpression of EC-SOD suppresses endothelial-cell-mediated LDL oxidation.
Reactive oxygen species have been proposed to play important roles in atherosclerosis. To investigate the protective role of extracellular superoxide dismutase (EC-SOD), its inhibition of endothelial-cell-mediated LDL oxidation was examined. We constructed the recombinant adenovirus AxCAEC-SOD expressing human EC-SOD by CAG promoter. Infection of endothelial cells with AxCAEC-SOD resulted in EC-SOD protein secretion in a dose-dependent manner and a decrease of endothelial-cell-derived superoxide production. Moreover, it was proven to coexist with heparan sulfate by immunohistochemical staining. Endothelial-cell-mediated LDL oxidation enhanced by ferric-sodium EDTA was inhibited by 47% in TBARS formation by AxCAEC-SOD infection. In agarose gel electrophoresis, AxCAEC-SOD decreased the negative charge of oxidized LDL by 50% and suppressed fragmentation of apolipoprotein B. These results suggested that human EC-SOD localized in the extracellular space and reduced endothelial-cell-mediated LDL oxidation. In subendothelial space, EC-SOD bound on heparan sulfate might suppress LDL oxidation through reduction of superoxide anion.
Takatsu
H
H
Second Department of Internal Medicine, Occupational Pneumology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Japan.
Tasaki
H
H
Kim
H N
HN
Ueda
S
S
Tsutsui
M
M
Yamashita
K
K
Toyokawa
T
T
Morimoto
Y
Y
Nakashima
Y
Y
Adachi
T
T
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D013552:Swine
D017931:DNA Primers; D006497:Heparan Sulfate; D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; D013482:Superoxide Dismutase