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Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16093-8. Epub 2002 Nov 27.

Biliverdin reductase: a major physiologic cytoprotectant.

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  • 1Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Bilirubin, an abundant pigment that causes jaundice, has long lacked any clear physiologic role. It arises from enzymatic reduction by biliverdin reductase of biliverdin, a product of heme oxygenase activity. Bilirubin is a potent antioxidant that we show can protect cells from a 10,000-fold excess of H2O2. We report that bilirubin is a major physiologic antioxidant cytoprotectant. Thus, cellular depletion of bilirubin by RNA interference markedly augments tissue levels of reactive oxygen species and causes apoptotic cell death. Depletion of glutathione, generally regarded as a physiologic antioxidant cytoprotectant, elicits lesser increases in reactive oxygen species and cell death. The potent physiologic antioxidant actions of bilirubin reflect an amplification cycle whereby bilirubin, acting as an antioxidant, is itself oxidized to biliverdin and then recycled by biliverdin reductase back to bilirubin. This redox cycle may constitute the principal physiologic function of bilirubin.

Comment in

  • The jaundice of the cell. [Proc Natl Acad Sci U S A. 2002]
PMID:
12456881
[PubMed - indexed for MEDLINE]
PMCID:
PMC138570
Free PMC Article

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