Glucose and free radicals impair the antioxidant properties of serum albumin

化学 牛血清白蛋白 糖基化 抗氧化剂 激进的 猝灭(荧光) 色氨酸 生物化学 过氧亚硝酸盐 血清白蛋白 阿玛多利重排 氧化磷酸化 色谱法 超氧化物 荧光 氨基酸 物理 受体 量子力学
作者
Emmanuel Bourdon,Nadine Loreau,Denis Blache
出处
期刊:The FASEB Journal [Wiley]
卷期号:13 (2): 233-244 被引量:285
标识
DOI:10.1096/fasebj.13.2.233
摘要

Epidemiological data consistently show that reduced levels of serum albumin, which is the most abundant protein in plasma, are associated with an increased mortality risk. Various biological properties evidenced by direct effects of the albumin molecule may explain its beneficial effects. The present work aimed to investigate in vitro whether glycation or free radicals or both factors would affect the antioxidant properties of bovine serum albumin (BSA). Glycation was performed by long-term incubations (60 days) of BSA with increasing concentrations of glucose (up to 500 mmol/l) at 37°C. Minimally oxidized BSA was obtained after controlled incubations of dialyzed BSA samples with a water-soluble free radical generator [2,2′ azo-bis(2-amidinopropane) HCl]. The glycation-mediated modifications and the free radical-induced conformational changes of BSA were monitored using intrinsic fluorescence measurements of the tryptophan residues and acrylamide as a quenching agent. Thiol groups, Amadori glycophore contents, and boronate binding were also measured. We found that the changes observed in the conformation of the BSA molecule were associated with modifications of its antioxidant properties. The latter were studied by the copper-mediated oxidation of human low density lipoproteins and the free radical-induced blood hemolysis test. Our data support the concept that oxidative-induced BSA modifications are important determinants in the antioxidant properties of BSA. Glycated BSA still behaved as an antioxidant but became pro-oxidant in the presence of copper, probably by generating oxygenated species. These data confirm the key role of metals ions in this process. Although these results warrant further in vivo investigations, we propose that, considering the poor glucose control found in diabetics as well as the key role of oxidative stress in vascular complications, glycation-mediated and free radical-induced impairment of the antioxidant properties of albumin might be important parameters in vascular complications encountered in diabetes.—Bourdon, E., Loreau, N., Blache, D. Glucose and free radicals impair the antioxidant properties of serum albumin. FASEB J. 13, 233–244 (1999)
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