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Biliverdin reductase: A major physiologic cytoprotectant
Journal article   Open access   Peer reviewed

Biliverdin reductase: A major physiologic cytoprotectant

David E. Barañano, Mahil Rao, Christopher D. Ferris and Solomon H. Snyder
Proceedings of the National Academy of Sciences - PNAS, Vol.99(25), pp.16093-16098
From the Cover
12/10/2002
DOI: 10.1073/pnas.252626999
PMCID: PMC138570
PMID: 12456881
url
https://doi.org/10.1073/pnas.252626999View
Published (Version of record) Open Access

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 H 2 O 2 . 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.
 Biological Sciences

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