Glutathione protects brain endothelial cells from hydrogen peroxide-induced oxidative stress by increasing nrf2 expression

Juhyun Song; So Mang Kang; Won Taek Lee; Kyung Ah Park; Kyoung Min Lee; Jong Eun Lee

doi:10.5607/en.2014.23.1.93

Glutathione protects brain endothelial cells from hydrogen peroxide-induced oxidative stress by increasing nrf2 expression

Exp Neurobiol. 2014 Mar;23(1):93-103. doi: 10.5607/en.2014.23.1.93. Epub 2014 Mar 27.

Authors

Juhyun Song¹, So Mang Kang², Won Taek Lee¹, Kyung Ah Park¹, Kyoung Min Lee³, Jong Eun Lee²

Affiliations

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

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