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Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation

Published online by Cambridge University Press:  08 March 2007

Khelifa Arab ,
Adrien Rossary ,
Laurent Soulère  and
Jean-Paul Steghens
Khelifa Arab
Affiliation:
Divison of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Adrien Rossary
Affiliation:
UF 21455, Oxidative Stress and Vitamins, Biochemistry Federation, E. Herriot Hospital, Lyon, France EA 3090, Claude Bernard University Lyon 1, Lyon, France
Laurent Soulère
Affiliation:
Laboratoire de Chime Organique, UMR CNRS-UCBL 5181, Institut National des sciences appliquées, 20 avenue A. Einstein, 69621 Villeurbanne, France
Jean-Paul Steghens*
Affiliation:
UF 21455, Oxidative Stress and Vitamins, Biochemistry Federation, E. Herriot Hospital, Lyon, France EA 3090, Claude Bernard University Lyon 1, Lyon, France
*
*Corresponding author: Dr Jean-Paul Steghens, fax +33 472 11 06 75, email [email protected]
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Abstract

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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 γ-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 γ-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.

Keywords

PUFAConjugated linoleic acidRedox statusAntioxidant responseGlutathioneCyclooxygenase-2Haemoxygenase-1Reactive oxygen speciesLipid peroxidation
Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 5 , November 2006 , pp. 811 - 819
Copyright
Copyright © The Nutrition Society 2006

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