title: Autotaxin protects microglial cells against oxidative stress.
abstract: Oxidative stress occurs when antioxidant defenses are overwhelmed by oxygen-reactive species and can lead to cellular damage, as seen in several neurodegenerative disorders. Microglia are specialized cells in the central nervous system that act as the first and main form of active immune defense in the response to pathological events. Autotaxin (ATX) plays an important role in the modulation of critical cellular functions, through its enzymatic production of lysophosphatidic acid (LPA). In this study, we investigated the potential role of ATX in the response of microglial cells to oxidative stress. We show that treatment of a microglial BV2 cell line with hydrogen peroxide (H(2)O(2)) stimulates ATX expression and LPA production. Stable overexpression of ATX inhibits microglial activation (CD11b expression) and protects against H(2)O(2)-treatment-induced cellular damage. This protective effect of ATX was partially reduced in the presence of the LPA-receptor antagonist Ki16425. ATX overexpression was also associated with a reduction in intracellular ROS formation, carbonylated protein accumulation, proteasomal activity, and catalase expression. Our results suggest that up-regulation of ATX expression in microglia could be a mechanism for protection against oxidative stress, thereby reducing inflammation in the nervous system.
authors.affiliation: Laboratoire de Biochimie et Génétique Moléculaire, Groupe d'Etude sur l'Inflammation Chronique et l'Obésité, Plateforme CYROI, Université de La Réunion, 97715 Saint Denis de La Réunion Cedex 09, France.
authors.forename: Rana
authors.initials: R
authors.lastname: Awada
authors.forename: Philippe
authors.initials: P
authors.lastname: Rondeau
authors.forename: Sandra
authors.initials: S
authors.lastname: Grès
authors.forename: Jean Sébastien
authors.initials: JS
authors.lastname: Saulnier-Blache
authors.forename: Christian
authors.initials: C
authors.lastname: Lefebvre d'Hellencourt
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourdon
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D019610:Cytoprotection; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000201:enzymology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050050:Protein Carbonylation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000099189:Lysophospholipase D
chemical_list: D002374:Catalase; D006861:Hydrogen Peroxide; D008246:Lysophospholipids; D052247:Nitric Oxide Synthase Type II; D016877:Oxidants; D010727:Phosphoric Diester Hydrolases; D046988:Proteasome Endopeptidase Complex; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid