GRP78 suppresses lipid peroxidation and promotes cellular antioxidant levels in glial cells following hydrogen peroxide exposure.
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
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.
Department of Anatomy and Cellular Biology, Basic Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Kaori
K
Suyama
Department of Orthopedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Masahiko
M
Watanabe
Department of Anatomy and Cellular Biology, Basic Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Kou
K
Sakabe
Department of Molecular Life Science, Basic Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Asako
A
Otomo
Tokai University Teaching and Research Support Center, Isehara, Kanagawa, Japan.
Yoshinori
Y
Okada
Department of Anatomy and Cellular Biology, Basic Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Hayato
H
Terayama
Department of Orthopedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Takeshi
T
Imai
Department of Orthopedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Joji
J
Mochida
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D015870:Gene Expression; D017930:Genes, Reporter; D005978:Glutathione / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015227:Lipid Peroxidation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D000091342:Endoplasmic Reticulum Chaperone BiP
D005978:Glutathione; D049452:Green Fluorescent Proteins; D006360:Heat-Shock Proteins; D006861:Hydrogen Peroxide; D016660:NAD(P)H Dehydrogenase (Quinone); D017382:Reactive Oxygen Species; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C507703:NQO1 protein, rat