Bilirubin and glutathione have complementary antioxidant and cytoprotective roles

Proceedings of the National Academy of Sciences of the United States of America - Tập 106 Số 13 - Trang 5171-5176 - 2009
Thomas W. Sedlak1,2, Masoumeh Saleh2, Daniel S. Higginson2, Bindu D. Paul2, Krishna R. Juluri2, Solomon H. Snyder3,1,2
1Department of Psychiatry and Behavioral Sciences
2The Solomon H. Snyder Department of Neuroscience, and
3Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 106 Số 13

5171-5176

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