Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 25, Pages 16093-16098Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.252626999
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- NIDA NIH HHS [DA-00266, F30 DA005900, K05 DA000074, DA-00074, DA05900, P50 DA000266] Funding Source: Medline
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Bilirubin, an abundant pigment that causes jaundice, has long lacked any clear physiologic role. It arises from enzymatic reduction by biliverclin 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 antioxiclant 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 antioxiclant cytoprotectant, elicits lesser increases in reactive oxygen species and cell death. The potent physiologic antioxiclant actions of bilirubin reflect an amplification cycle whereby bilirubin, acting as an antioxiclant, is itself oxidized to biliverclin and then recycled by biliverdin reductase back to bilirubin. This redox cycle may constitute the principal physiologic function of bilirubin.
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