Liver X Receptor exerts a protective effect against the oxidative stress in the peripheral nerve

Mehdi Hichor,Didier Borderie,Venkat Krishnan Sundaram,Charbel Massaad,Jean Bastin,Marin Manuel,Assaad A Eid,Stéphanie A Eid,Julien Grenier,Patrice X Petit,Ronza Abdel-Rassoul

doi:10.1038/s41598-018-20980-3

Abstract

Reactive oxygen species (ROS) modify proteins and lipids leading to deleterious outcomes. Thus, maintaining their homeostatic levels is vital. This study highlights the endogenous role of LXRs (LXRα and β) in the regulation of oxidative stress in peripheral nerves. We report that the genetic ablation of both LXR isoforms in mice (LXRdKO) provokes significant locomotor defects correlated with enhanced anion superoxide production, lipid oxidization and protein carbonylation in the sciatic nerves despite the activation of Nrf2-dependant antioxidant response. Interestingly, the reactive oxygen species scavenger N-acetylcysteine counteracts behavioral, electrophysical, ultrastructural and biochemical alterations in LXRdKO mice. Furthermore, Schwann cells in culture pretreated with LXR agonist, TO901317, exhibit improved defenses against oxidative stress generated by tert-butyl hydroperoxide, implying that LXRs play an important role in maintaining the redox homeostasis in the peripheral nervous system. Thus, LXR activation could be a promising strategy to protect from alteration of peripheral myelin resulting from a disturbance of redox homeostasis in Schwann cell.

Highlights

To cite this version: Mehdi Hichor, Venkat Sundaram, Stéphanie Eid, Ronza Abdel-Rassoul, Patrice Petit, et al
We report that the genetic ablation of both LXR isoforms in mice (LXRdKO) provokes significant locomotor defects correlated with enhanced anion superoxide production, lipid oxidization and protein carbonylation in the sciatic nerves despite the activation of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependant antioxidant response
Schwann cells in culture pretreated with LXR agonist, TO901317, exhibit improved defenses against oxidative stress generated by tert-butyl hydroperoxide, implying that LXRs play an important role in maintaining the redox homeostasis in the peripheral nervous system

Summary

Introduction

To cite this version: Mehdi Hichor, Venkat Sundaram, Stéphanie Eid, Ronza Abdel-Rassoul, Patrice Petit, et al. HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. OPEN Liver X Receptor exerts a protective effect against the oxidative stress in the peripheral nerve. Reactive oxygen species (ROS) modify proteins and lipids leading to deleterious outcomes. We report that the genetic ablation of both LXR isoforms in mice (LXRdKO) provokes significant locomotor defects correlated with enhanced anion superoxide production, lipid oxidization and protein carbonylation in the sciatic nerves despite the activation of Nrf2-dependant antioxidant response. Schwann cells in culture pretreated with LXR agonist, TO901317, exhibit improved defenses against oxidative stress generated by tert-butyl hydroperoxide, implying that LXRs play an important role in maintaining the redox homeostasis in the peripheral nervous system. LXR activation could be a promising strategy to protect from alteration of peripheral myelin resulting from a disturbance of redox homeostasis in Schwann cell

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