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Original Article

Exp Neurobiol 2014; 23(1): 93-103

Published online March 30, 2014

https://doi.org/10.5607/en.2014.23.1.93

© The Korean Society for Brain and Neural Sciences

Glutathione Protects Brain Endothelial Cells from Hydrogen Peroxide-Induced Oxidative Stress by Increasing Nrf2 Expression

Juhyun Song1, So Mang Kang1,2, Won Taek Lee1, Kyung Ah Park1, Kyoung Min Lee3 and Jong Eun Lee1,2*

1Department of Anatomy, Yonsei University College of Medicine, 2BK21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-572, 3Department of Neurology, Seoul National University College of Medicine, Seoul 110-744, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2228-1646, 1659, FAX: 82-2-365-0700
e-mail: jelee@yuhs.ac

Received: February 25, 2014; Revised: March 5, 2014; Accepted: March 5, 2014

Abstract

Glutathione (GSH) protects cells against oxidative stress by playing an antioxidant role. Protecting brain endothelial cells under oxidative stress is key to treating cerebrovascular diseases and neurodegenerative diseases including Alzheimer's disease and Huntington's disease. In present study, we investigated the protective effect of GSH on brain endothelial cells against hydrogen peroxide (H2O2). We showed that GSH attenuates H2O2-induced production of nitric oxide (NO), reactive oxygen species (ROS), and 8-Oxo-2'-deoxyguanosine (8-OHdG), an oxidized form of deoxiguanosine. GSH also prevents H2O2-induced reduction of tight junction proteins. Finally, GSH increases the level of nuclear factor erythroid 2-related factor 2 (Nrf2) and activates Nrf2-mediated signaling pathways. Thus, GSH is a promising target to protect brain endothelial cells in conditions of brain injury and disease.

Keywords: glutathione (GSH), murine brain endothelial cells (bEnd.3 cells), apoptosis, hydrogen peroxide (H2O2), Reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2)