Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation.
Enhancement of the redox status of cells is a cytoprotective strategy against oxidative damage. We recently showed that DHA upregulates glutathione (GSH) content via an induction of its related enzymes gamma-glutamylcysteine ligase and glutathione reductase. In the present study, we investigated the effects of eight other fatty acids on the redox status and lipid peroxidation of human fibroblasts. After 48 h, only arachidonic acid and conjugated linoleic acid (CLA) enhanced GSH content through an induction of gamma-glutamylcysteine ligase. CLA was more potent than arachidonic acid in inducing GSH synthesis. For all the fatty acids tested, lipoperoxidation, estimated by cell malondialdehyde measurement, did not differ from that of controls at 48 h but dramatically increased at 7 d, except for CLA. Lipoperoxidation is associated at 7 d with a high level of reactive oxygen species and with increased haemoxygenase-1 and cyclooxygenase-2 mRNA expression. As demonstrated by a tert-butylhydroperoxide cytotoxicity test, the GSH synthesis obtained with arachidonic acid is not sufficient to protect the cells, whereas this protective effect was obvious with CLA at 48 h as well as at 7 d. The present results show that CLA is the only PUFA able to induce GSH synthesis without any change in oxidative balance, whereas an upregulation of cyclooxygenase-2 by other PUFA is concomitant with an overproduction of malondialdehyde and reactive oxygen species. The particular hairpin conformation obtained for CLA by molecular modelling could account for this specific biological effect.
Arab
Khelifa
K
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Rossary
Adrien
A
Soulère
Laurent
L
Steghens
Jean-Paul
JP
D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005227:Fatty Acids / Q000008:administration & dosage* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D005978:Glutathione / Q000096:biosynthesis*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000032:analysis; D008958:Models, Molecular; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism
D003470:Culture Media; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D005978:Glutathione