GRP78 suppresses lipid peroxidation and promotes cellular antioxidant levels in glial cells following hydrogen peroxide exposure

PLoS One. 2014 Jan 24;9(1):e86951. doi: 10.1371/journal.pone.0086951. eCollection 2014.

Abstract

Oxidative stress, caused by the over production of reactive oxygen species (ROS), has been shown to contribute to cell damage associated with neurotrauma and neurodegenerative diseases. ROS mediates cell damage either through direct oxidation of lipids, proteins and DNA or by acting as signaling molecules to trigger cellular apoptotic pathways. The 78 kDa glucose-regulated protein (GRP78) is an ER chaperone that has been suggested to protect cells against ROS-induced damage. However, the protective mechanism of GRP78 remains unclear. In this study, we used C6 glioma cells transiently overexpressing GRP78 to investigate the protective effect of GRP78 against oxidative stress (hydrogen peroxide)-induced injury. Our results showed that the overexpression of GRP78 significantly protected cells from ROS-induced cell damage when compared to non-GRP78 overexpressing cells, which was most likely due to GRP78-overexpressing cells having higher levels of glutathione (GSH) and

Nad(p)h: quinone oxidoreductase 1 (NQO1), two antioxidants that protect cells against oxidative stress. Although hydrogen peroxide treatment increased lipid peroxidation in non-GRP78 overexpressing cells, this increase was significantly reduced in GRP78-overexpressing cells. Overall, these results indicate that GRP78 plays an important role in protecting glial cells against oxidative stress via regulating the expression of GSH and NQO1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival
  • Gene Expression
  • Genes, Reporter
  • Glutathione / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Hydrogen Peroxide / pharmacology*
  • Lipid Peroxidation
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • Neuroglia / cytology
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Reactive Oxygen Species
  • Green Fluorescent Proteins
  • Hydrogen Peroxide
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, rat
  • Glutathione

Grants and funding

This study was supported in part by the Research and Study Program of Tokai University Educational System General Research Organization and 2012 Tokai University School of Medicine Research Aid.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.