Consequences of PPARα Invalidation on Glutathione Synthesis: Interactions with Dietary Fatty Acids. (12th September 2011)

• Record Type: Journal Article
• Authors: Guelzim, Najoua; Huneau, Jean-François; Mathé, Véronique; Quignard-Boulangé, Annie; Martin, Pascal G.; Tomé, Daniel; Hermier, Dominique
• Other Names: Mandard Stephane Academic Editor.
• Is Part Of: PPAR research. Volume 2011(2011)
• Publication Date: 2011-09-12
• Subjects: Peroxisomes -- Periodicals; Peroxisomal disorders -- Periodicals; 571.65505
• DOI: 10.1155/2011/256186
• Languages: English
• ISSNs: 1687-4757

Abstract

Abstract : Glutathione (GSH) derives from cysteine and plays a key role in redox status. GSH synthesis is determined mainly by cysteine availability and γ -glutamate cysteine ligase ( γ GCL) activity. Because PPAR α activation is known to control the metabolism of certain amino acids, GSH synthesis from cysteine and related metabolisms were explored in wild-type (WT) and PPAR α -null (KO) mice, fed diets containing either saturated (COCO diet) or 18 : 3 n-3, LIN diet. In mice fed the COCO diet, but not in those fed the LIN diet, PPAR α deficiency enhanced hepatic GSH content and γ GCL activity, superoxide dismutase 2 mRNA levels, and plasma uric acid concentration, suggesting an oxidative stress. In addition, in WT mice, the LIN diet increased the hepatic GSH pool, without effect on γ GCL activity, or change in target gene expression, which rules out a direct effect of PPAR α . This suggests that dietary 18 : 3 n-3 may regulate GSH metabolism and thus mitigate the deleterious effects of PPAR α deficiency on redox status, without direct PPAR α activation.