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Inhibition of oxygen toxicity by targeting Superoxide dismutase to endothelial cell surface
Author(s) -
Inoue Masayasu,
Watanabe Nobukazu,
Morino Yoshimasa,
Tanaka Yoshikazu,
Amachi Teruo,
Sasaki Junzo
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)81126-9
Subject(s) - superoxide dismutase , endothelial stem cell , chemistry , superoxide , biochemistry , reactive oxygen species , dismutase , microbiology and biotechnology , intracellular , oxidative stress , enzyme , biology , in vitro
Since enzymes that degrade reactive oxygens, such as Superoxide dismutase (SOD), are significantly lower in plasma than in intracellular compartments, cell surface membranes should be protected against hazardous oxygens particularly when animals are challenged with oxidative stress. To minimize oxygen toxicity on endothelial cell surface, a fusion gene consisting of cDNA coding human Cu 2+ /Zn 2+ ‐SOD and heparin‐binding peptide was constructed and expressed in yeast. The resulting enzyme (HB‐SOD) bound to a heparin‐Sepharose column and cultured endothelial cells; binding was inhibited either by high NaCl concentrations or heparin. When injected intravenously, HB‐SOD predominantly bound to vascular endothelial cell surface. Carrageenin‐induced paw edema and cold‐induced brain edema of the rat were markedly inhibited by a single dose of HB‐SOD. These results suggest that Superoxide radical and/or its metabolite(s) occurring at or near the outer surface of vascular endothelial cells might play a critical role in the pathogenesis of vasogenic edema.