title: Docosahexaenoic acid enhances the antioxidant response of human fibroblasts by upregulating gamma-glutamyl-cysteinyl ligase and glutathione reductase.
abstract: 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 micromol/l in a model of human fibroblast cell culture. A dose-response effect, roughly linear, was checked for DHA between 0 and 60 micromol/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.
authors.affiliation: EA 3090, Claude Bernard University Lyon 1, France.
authors.forename: Khelifa
authors.initials: K
authors.lastname: Arab
authors.forename: Adrien
authors.initials: A
authors.lastname: Rossary
authors.forename: Françoise
authors.initials: F
authors.lastname: Flourié
authors.forename: Yves
authors.initials: Y
authors.lastname: Tourneur
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Steghens
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000032:analysis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000032:analysis; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D004281:Docosahexaenoic Acids; D006419:Heme Oxygenase (Decyclizing); D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase