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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
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 jean-paul.steghens@chu-lyon.fr
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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.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Arab, K, Rossary, A, Flourie, F, Tourner, Y & Steghens, JP (2006) Docosahexaenoic acid enhances the antioxidant response of human fibroblasts by upregulating γ-glutamyl-cysteinyl ligase and glutathione reductase. Br J Nutr 95, 1826.CrossRefGoogle ScholarPubMed
Arab, K & Steghens, JP (2004) Plasma lipid hydroperoxides measurement by an automated xylenol orange method. Anal Biochem 325, 158163.CrossRefGoogle ScholarPubMed
Carter, WO, Narayanan, PK & Robinson, JP (1994) Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells. J Leukoc Biol 55, 253258.Google ScholarPubMed
Chan, DC, Watts, GF, Mori, TA, Barrett, PH, Redgrave, TG & Beilin, LJ (2003) Randomized controlled trial of the effect of n-3 fatty acid supplementation on the metabolism of apolipoprotein B-100 and chylomicron remnants in men with visceral obesity. Am J Clin Nut. 77, 300307.CrossRefGoogle Scholar
Chik, K, Flourie, F, Arab, K & Steghens, JP (2005) Kinetic measurement by LC/MS of gamma-glutamylcysteine ligase activity. J Chromatogr B 827, 3238.CrossRefGoogle Scholar
Gao, X, Dinkova-Kostova, AT & Talalay, P (2001) Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: the indirect antioxidant effects of sulforaphane. PNAS 98, 1522115226.CrossRefGoogle ScholarPubMed
Higdon, JV, Liu, J, Du, SH, Morrow, JD, Ames, BN & Wander, RC (2000) Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)-isoprostanes. Am J Clin Nutr 72, 714722.CrossRefGoogle Scholar
Hill-Kapturczak, N, Voakes, C, Garcia, J, Visner, G, Nick, HS & Agarwal, A (2003) A cis-acting region regulates oxidized lipid-mediated induction of the human heme oxygenase-1 gene in endothelial cells. Arterioscler Thromb Vasc Biol 23, 14161422.CrossRefGoogle ScholarPubMed
Ishii, T, Itoh, K, Ruiz, E, Leake, DS, Unoki, H, Yamamoto, M & Mann, GE (2004) Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages: activation by oxidatively modified LDL and 4-hydroxynonenal. Circ Res 94, 609616.CrossRefGoogle ScholarPubMed
Jump, DB (2002) The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 277, 87558758.CrossRefGoogle ScholarPubMed
Kim, BR, Hu, R, Keum, YS, Hebbar, V, Shen, G, Nair, SS & Kong, AN (2003) Effects of glutathione on antioxidant response element-mediated gene expression and apoptosis elicited by sulforaphane. Cancer Res 63, 75207525.Google ScholarPubMed
Kim, YS, Zhuang, H, Koehler, RC & Dore, S (2005) Distinct protective mechanisms of HO-1 and HO-2 against hydroperoxide-induced cytotoxicity. Free Radic Biol Med 38, 8592.CrossRefGoogle ScholarPubMed
Kumagai, T, Matsukawa, N, Kaneko, Y, Kusumi, Y, Mitsumata, M & Uchida, K (2004) A lipid peroxidation-derived inflammatory mediator: identification of 4-hydroxy-2-nonenal as a potential inducer of cyclooxygenase-2 in macrophages. J Biol Chem 279, 4838948396.CrossRefGoogle ScholarPubMed
Kuniyasu, H, Yoshida, K, Sasaki, T, Sasahira, T, Fujii, K & Ohmori, H (2006) Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells. Int J Cancer 118, 571576.CrossRefGoogle ScholarPubMed
Laidlaw, M & Holub, BJ (2003) Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am J Clin Nutr 77, 3742.CrossRefGoogle ScholarPubMed
Lee, JM, Calkins, MJ, Chan, K, Kan, YW & Johnson, JA (2003) Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 278, 1202912038.CrossRefGoogle ScholarPubMed
Lee, SH, Williams, MV, Dubois, RN & Blair, IA (2005) Cyclooxygenase-2-mediated DNA damage. J Biol Chem 280, 2833728346.CrossRefGoogle ScholarPubMed
Leung, L, Kwong, M, Hou, S, Lee, C & Chan, JY (2003) Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. J Biol Chem 278, 4802148029.CrossRefGoogle ScholarPubMed
Levonen, AL, Landar, A, Ramachandran, A, Ceaser, EK, Dickinson, DA, Zanoni, G, Morrow, JD & Darley-Usmar, VM (2004) Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products. Biochem J 378, Pt 2, 373382.CrossRefGoogle ScholarPubMed
Liu, Q, Smith, MA & Avila, J (2005) Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations. Free Radic Biol Med 38, 746754.CrossRefGoogle ScholarPubMed
Lynch, AM, Moore, M, Craig, S, Lonergan, PE, Martin, DS & Lynch, MA (2003) Analysis of interleukin-1 beta-induced cell signaling activation in rat hippocampus following exposure to gamma irradiation. Protective effect of eicosapentaenoic acid. J Biol Chem 278, 5107551084.CrossRefGoogle ScholarPubMed
Maheo, K, Vibet, S, Steghens, JP, Dartigeas, C, Lehman, M, Bougnoux, P & Gore, J (2005) Differential sensitization of cancer cells to doxorubicin by DHA: A role for lipoperoxidation. Free Radic Biol Med 39, 742751.CrossRefGoogle ScholarPubMed
Manna, SK, Kuo, MT & Aggarwal, BB (1999) Overexpression of gamma-glutamylcysteine synthetase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappa B and activator protein-1. Oncogene 18, 43714382.CrossRefGoogle ScholarPubMed
Meister, A (1983) Selective modification of glutathione metabolism. Science 20, 472477.CrossRefGoogle Scholar
Mori, TA, Woodman, RJ, Burke, V, Puddey, IB, Croft, KD & Beilin, LJ (2003) Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radic Biol Med 35, 772781.CrossRefGoogle ScholarPubMed
Mosmann, T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65, 5563.CrossRefGoogle ScholarPubMed
Mukherjee, PK, Marcheselli, VL, Serhan, CN & Bazan, NG (2004) Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. PNAS 101, 84918496.CrossRefGoogle ScholarPubMed
Nanji, AA, Jokelainen, K, Fotouhinia, M, Rahemtulla, A, Thomas, P, Tipoe, GL, Su, GL & Dannenberg, AJ (2001) Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines. Am J Physiol Gastrointest Liver Physiol 281, G1348G1356.CrossRefGoogle ScholarPubMed
Ng, Y, Barhoumi, R, Tjalkens, RB, Fan, YY, Kolar, S, Wang, N, Lupton, JR & Chapkin, RS (2005) The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes. Carcinogenesis 26, 19141921.CrossRefGoogle ScholarPubMed
Obata, T, Nagakura, T, Masaki, T, Maekawa, K & Yamashita, K (1999) Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells. Clin Exp Allergy 29, 11291135.CrossRefGoogle ScholarPubMed
Oostenbrug, GS, Mensink, RP & Hornstra, G (1994) Effects of fish oil and vitamin E supplementation on copper-catalysed oxidation of human low density lipoprotein in vitro. Eur J Clin Nutr 48, 895898.Google ScholarPubMed
Peiro, G, Alary, J, Cravedi, JP, Rathahao, E, Steghens, JP & Gueraud, F (2005) Dihydroxynonene mercapturic acid, a urinary metabolite of 4-hydroxynonenal, as a biomarker of lipid peroxidation. Biofactors 24, 8996.CrossRefGoogle ScholarPubMed
Pepe, S & McLennan, PL (2002) Cardiac membrane fatty acid composition modulates myocardial oxygen consumption and postischemic recovery of contractile function. Circulation 105, 23032308.CrossRefGoogle ScholarPubMed
Rahman, I (2005) Regulation of glutathione in inflammation and chronic lung diseases. Mutat Res 579, 5880.CrossRefGoogle ScholarPubMed
Ringborn, T, Huss, U, Stenholm, A, Flock, S, Skattebol, L, Perera, P & Bohlin, L (2001) Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod 64, 745749.CrossRefGoogle Scholar
Ryder, JW, Portocarrero, CP & Song, XM (2001) Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes 50, 11491157.CrossRefGoogle ScholarPubMed
Smith, WL, DeWitt, DL & Garavito, RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69, 145182.CrossRefGoogle ScholarPubMed
Song, JH, Fujimoto, K & Miyazawa, T (2000) Polyunsaturated (n-3) fatty acids susceptible to peroxidation are increased in plasma and tissue lipids of rats fed docosahexaenoic acid-containing oils. J Nutr 130, 30283033.CrossRefGoogle ScholarPubMed
Steghens, JP, Flourie, F, Arab, K & Collombel, C (2003) Fast liquid chromatography-mass spectrometry glutathione measurement in whole blood: micromolar GSSG is a sample preparation artifact. J Chromatogr B 798, 343349.CrossRefGoogle ScholarPubMed
Storey, A, McArdle, F, Friedmann, PS, Jackson, MJ & Rhodes, LE (2005) Eicosapentaenoic acid and docosahexaenoic acid reduce UVB- and TNF-alpha-induced IL-8 secretion in keratinocytes and UVB-induced IL-8 in fibroblasts. J Invest Dermatol 124, 248255.CrossRefGoogle ScholarPubMed
Suh, JH, Shenvi, SV, Dixon, BM, Liu, H, Jaiswal, AK, Liu, RM & Hagen, TM (2004) Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. PNAS 101, 33813386.CrossRefGoogle ScholarPubMed
Terasawa, Y, Ladha, Z, Leonard, SW, Morrow, JD, Newland, D, Sanan, D, Packer, L, Traber, MG & Farese, RV Jr (2000) Increased atherosclerosis in hyperlipidemic mice deficient in alpha-tocopherol transfer protein and vitamin E. PNAS 97, 1383013834.CrossRefGoogle ScholarPubMed
Urata, Y, Yamamoto, H, Goto, S, Tsushima, H, Akazawa, S, Yamashita, S, Nagataki, S & Kondo, T (1996) Long exposure to high glucose concentration impairs the responsive expression of gamma-glutamylcysteine synthetase by interleukin-1beta and tumor necrosis factor-alpha in mouse endothelial cells. J Biol Chem 271, 1514615152.CrossRefGoogle ScholarPubMed
Utomo, A, Jiang, X, Furuta, S, Yun, J, Levin, DS, Wang, YC, Desai, KV, Green, JE, Chen, PL & Lee, WH (2004) Identification of a novel putative non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) essential for alleviating oxidative stress generated from polyunsaturated fatty acids in breast cancer cells. J Biol Chem 279, 4352243529.CrossRefGoogle ScholarPubMed
Wild, AC, Moinova, HR & Mulcahy, RT (1999) Regulation of gamma-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J Biol Chem 274, 3362733636.CrossRefGoogle ScholarPubMed
Wu, X, Bishopric, NH, Discher, DJ, Murphy, BJ & Webster, KA (1996) Physical and functional sensitivity of zinc finger transcription factors to redox change. Mol Cell Biol 16, 10351046.CrossRefGoogle ScholarPubMed
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Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation
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