文章基本信息

标题：Bilirubin and glutathione have complementary antioxidant and cytoprotective roles
本地全文：下载
作者：Thomas W. Sedlak ; Masoumeh Saleh ; Daniel S. Higginson 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：13
页码：5171-5176
DOI：10.1073/pnas.0813132106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Glutathione (GSH) and bilirubin are prominent endogenous antioxidant cytoprotectants. Despite tissue levels that are thousands of times lower than GSH, bilirubin is effective because of the biosynthetic cycle wherein it is generated from biliverdin by biliverdin reductase (BVR). When bilirubin acts as an antioxidant, it is oxidized to biliverdin, which is immediately reduced by BVR to bilirubin. Why does the body employ both of these 2 distinct antioxidant systems? We show that the water-soluble GSH primarily protects water soluble proteins, whereas the lipophilic bilirubin protects lipids from oxidation. Mice with deletion of heme oxygenase-2, which generates biliverdin, display greater lipid than protein oxidation, while the reverse holds for GSH depletion. RNA interference depletion of BVR increases oxidation of lipids more than protein. Depletion of BVR or GSH augments cell death in an oxidant-specific fashion.
关键词：apoptosis ; biliverdin ; cell death ; heme oxygenase ; neuroprotection