Proteomic analysis of the effects of Nur77 on lipopolysaccharide-induced microglial activation

Neurosci Lett. 2017 Oct 17:659:33-43. doi: 10.1016/j.neulet.2017.07.022. Epub 2017 Jul 17.

Abstract

Microglia are critical components of the immune response in the central nervous system. Our study aims to explore potential role of Nur77 in lipopolysaccharide (LPS)-induced microglial activation. Primary wild-type and Nur77-/- microglia were stimulated with LPS and protein extracts were detected via mass spectrometry. Q-PCR and western blotting were performed to validate candidate proteins. A total of 2004 proteins were identified, with 749 and 677 significantly differentially expressed proteins in wild-type and Nur77-/- microglia in resting and activated states, respectively. Signaling pathway analysis showed that significantly differentially expressed proteins in LPS-treated Nur77-/- microglia were present in important signaling pathways of microglial activation, including the Toll-like receptor signaling pathway, the MAPK signaling pathway, FcγR-mediated phagocytosis, and chemokine signaling pathways. Furthermore, we found that Nur77 could be the upstream protein of the vav1 and ERK1/2 signaling pathway. This study provided new insights into the understanding the mechanisms of the effects of Nur77 on LPS-activated microglia.

Keywords: Lipopolysaccharide; Microglial activation; Nur77; Proteomics.

MeSH terms

  • Animals
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Transgenic
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / immunology
  • Microglia / metabolism*
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
  • Proteomics*
  • Signal Transduction / drug effects

Substances

  • Lipopolysaccharides
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1