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标题：Conjugated linoleic acid enhances glutathione synthesis and attenuates pathological signs in MRL/MpJ-Faslpr mice
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作者：Bergamo, Paolo ; Luongo, Diomira ; Maurano, Francesco 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2006
卷号：47
期号：11
页码：2382-2391
DOI：10.1194/jlr.M600187-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Conjugated linoleic acid (CLA), a naturally occurring peroxisomeproliferator-activated receptor ${gamma}$ (PPAR ${gamma}$ ) ligand, exhibits proapoptotic,immunomodulatory, and anticancer properties. In this study,we examined the biological effects of CLA administration inthe MRL/MpJ-Fas^lpr mouse, an animal model of systemic lupuserythematosus (SLE). We found that CLA exerted apparently opposedactivities in in vitro experiments, depending on its concentration:100 µM CLA downregulated IFN ${gamma}$ synthesis and cell proliferationof splenocytes, in association with apoptosis induction anda decrease of intracellular thiols (GSH + GSSG), whereas 25µM CLA did not significantly influence cell proliferationbut enhanced the expression of ${gamma}$ -glutamylcysteine ligase catalyticsubunit (GCLC) and intracellular GSH concentration. Interestingly,the antiproliferative effect at 100 µM was not inhibitedby the PPAR ${gamma}$ antagonist GW9662. In vivo, CLA administration drasticallyreduced SLE signs (splenomegaly, autoantibodies, and cytokinesynthesis), a condition paralleled by the enhancement of GCLCexpression and intracellular GSH content. Moreover, CLA administrationsignificantly downregulated nuclear factor ${kappa}$ B activity independentof PPAR ${gamma}$ activation and apoptosis induction. In conclusion, enhancedGSH content and GCLC expression in CLA-treated mice suggesta novel biochemical mechanism underlying its immunomodulatoryactivity and the beneficial effects on murine SLE signs. Supplementary key words autoimmune disease • peroxisome proliferator-activated receptor ${gamma}$ • ${gamma}$ -glutamylcysteine ligase Abbreviations: anti-dsDNA, anti-double-stranded DNA; anti-tTG, anti-tissue transglutaminase; CLA, conjugated linoleic acid; 15dPGJ₂, 15-deoxy- ${Delta}$ 12,14-prostaglandin J₂; GCLC, ${gamma}$ -glutamylcysteine ligase catalytic subunit; IL, interleukin; MRL/lpr, MRL/MpJ-Fas^lpr; NF ${kappa}$ B, nuclear factor ${kappa}$ B; O₂^•–, superoxide anion radical; PPAR ${gamma}$ peroxisome proliferator-activated receptor ${gamma}$ ; ROS, reactive oxygen species; SLE, systemic lupus erythematosus