Inhibition of oxygen toxicity by targeting Superoxide dismutase to endothelial cell surface

FEBS Letters

Morino, Yoshimasa¹  Amachi, Teruo²  Inoue, Masayasu¹  Watanabe, Nobukazu¹  Tanaka, Yoshikazu²  Sasaki, Junzo³ 

[1] Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan;Institute for Fundamental Research Center, Santory, Ltd, Shimamoto-cho, Mishima-gun, Osaka 618, Japan;Department of Anatomy, Okayama University Medical School, 2-5-1 Shikatachyo, Okayama 700, Japan

关键词: Superoxide dismutase;    Gene engineering;    Oxygen toxicity;    Heparin;    Endothelial cell;    Ischemic heart disease;   

DOI  :  10.1016/0014-5793(90)81126-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Cu²⁺/Zn²⁺-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.

【 授权许可】

Unknown