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

• Published in: British journal of nutrition Vol. 95; no. 1; pp. 18 - 26
• Main Authors: Arab, Khelifa, Rossary, Adrien, Flourié, Françoise, Tourneur, Yves, Steghens, Jean-Paul
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.01.2006; Cambridge University Press (CUP)
• Subjects: antioxidant activity; antioxidants; Antioxidants - metabolism; Biological and medical sciences; cell culture; Cells, Cultured; Chemoprevention; Docosahexaenoic acid; Docosahexaenoic Acids - metabolism; Docosahexaenoic Acids - pharmacology; dose response; Dose-Response Relationship, Drug; enzyme activity; Fatty Acids - analysis; Feeding. Feeding behavior; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; free radicals; Fundamental and applied biological sciences. Psychology; Glutamate-Cysteine Ligase - metabolism; Glutathione; glutathione reductase (NADPH); Glutathione Reductase - metabolism; glutathione transferase; Glutathione Transferase - metabolism; Heme Oxygenase (Decyclizing) - metabolism; Humans; Life Sciences; ligases; omega-3 fatty acids; Oxidation-Reduction; Oxidative stress; Oxidative Stress - physiology; Reactive Oxygen Species - analysis; redox reactions; RNA, Messenger - analysis; Sulfhydryl Compounds - metabolism; Thiol-redox status; thiols; Time Factors; Up-Regulation - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Fibroblasts; Oxidative stress; Docosahexaenoic acid; Chemoprevention; Thiol-redox status; Glutathione; Human; Thiol; Enzyme; Antioxidant; Vertebrata; Mammalia; Ligases; Docosahexaenoic acid: Chemoprevention: Thiol-redox status: Fibroblasts: Glutathione: Oxidative stress; Oxidoreductases; Fibroblast; Reductase
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1079/BJN20051626

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 30µmol/l in a model of human fibroblast cell culture. A dose–response effect, roughly linear, was checked for DHA between 0 and 60µmol/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 4h after the beginning of the experiment, the large increase in the GSH content was associated with elevated catalytic activities of γ-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 γ-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.