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

Sci Rep. 2018 Feb 6;8(1):2524. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Homeostasis*
  • Hydrocarbons, Fluorinated / chemistry
  • Lipid Metabolism
  • Liver X Receptors / antagonists & inhibitors
  • Liver X Receptors / genetics
  • Liver X Receptors / physiology*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin Sheath / metabolism*
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction
  • Oxidative Stress*
  • Protein Carbonylation
  • Reactive Oxygen Species / metabolism
  • Schwann Cells* / cytology
  • Schwann Cells* / metabolism
  • Sciatic Nerve* / cytology
  • Sciatic Nerve* / metabolism
  • Sulfonamides / chemistry
  • tert-Butylhydroperoxide / chemistry

Substances

  • Hydrocarbons, Fluorinated
  • Liver X Receptors
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Nr1h3 protein, mouse
  • Reactive Oxygen Species
  • Sulfonamides
  • TO-901317
  • tert-Butylhydroperoxide