Docosahexaenoic acid enhances the antioxidant response of human fibroblasts by upregulating γ-glutamyl-cysteinyl ligase and glutathione reductase

被引:67
作者
Arab, K
Rossary, A
Flourié, F
Tourneur, Y
Steghens, JP [1 ]
机构
[1] E Herriot Hosp, UF Oxidat Stress & Vitamins 21455, Biochem Federat, Lyon, France
[2] Univ Lyon 1, EA 3090, F-69365 Lyon, France
[3] Univ Lyon 1, Fac Pharm, Quantimetry Ctr, F-69365 Lyon, France
关键词
docosahexaenoic acid; chemoprevention; thiol-redox status; fibroblasts; glutathione; oxidative stress;
D O I
10.1079/BJN20051626
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
The chemopreventive effects of dietary n-3 PUFA in various pathologies has so far remained controversial, and we were interested in studying their potential influence on cell redox status. DHA (22 : 6n-3), a typical highly unsaturated n-3 PUFA, was used at 30 mu mol/l in a model of human fibroblast cell culture. A dose-response effect, roughly linear, was checked for DHA between 0 and 60 mu mol/l, and was accompanied by a large increase in intracellular GSH content. A time course study of this effect shows that, after a short fall, as soon as 4 h after the beginning of the experiment, the large increase in the GSH content was associated with elevated catalytic activities of gamma-glutamyl-cysteinyl ligase, glutathione reductase and glutathione S-transferase. This coordinated response is characteristic of an antioxidant response and was confirmed by the induction of expression of mRNA for gamma-glutamyl-cysteinyl ligase, glutathione reductase and haem-oxygenase. This large increase in the GSH content contributes to decreasing the reactive oxygen species level, as assessed by the decreased accumulation of dichlorofluorescein inside cells. To our knowledge, this is the first report on a specific and potent effect of DHA for decreasing the oxidative stress of human fibroblasts.
引用
收藏
页码:18 / 26
页数:9
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