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Related Experiment Videos

Biliverdin reductase: a major physiologic cytoprotectant.

David E Baranano1, Mahil Rao, Christopher D Ferris

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

Proceedings of the National Academy of Sciences of the United States of America
|November 29, 2002
PubMed
Summary

Bilirubin, a pigment causing jaundice, acts as a powerful physiologic antioxidant. It protects cells from oxidative stress via a redox cycle, revealing its principal function.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • Bilirubin, a byproduct of heme metabolism, is known for causing jaundice but lacks a defined physiological role.
  • Heme oxygenase activity produces biliverdin, which is then reduced to bilirubin by biliverdin reductase.
  • The antioxidant properties of bilirubin have been recognized, but its specific physiological function remains unclear.

Purpose of the Study:

  • To investigate the physiological role of bilirubin as an antioxidant.
  • To determine if bilirubin functions as a cytoprotectant against oxidative stress.
  • To elucidate the mechanism underlying bilirubin's antioxidant activity.

Main Methods:

  • Utilized RNA interference to deplete cellular bilirubin levels.
  • Assessed reactive oxygen species (ROS) levels and apoptotic cell death.

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  • Compared the effects of bilirubin depletion with glutathione depletion.

    • Main Results:

    • Cellular depletion of bilirubin significantly increased reactive oxygen species and induced apoptotic cell death.
    • Bilirubin demonstrated potent cytoprotective effects against hydrogen peroxide (H2O2)-induced oxidative stress.
    • The antioxidant action of bilirubin involves a redox cycle where it is oxidized to biliverdin and then recycled by biliverdin reductase.

    Conclusions:

    • Bilirubin is a major physiological antioxidant and cytoprotectant.
    • The identified redox cycle of bilirubin and biliverdin reductase may represent bilirubin's principal physiological function.
    • Bilirubin's role as an antioxidant is more significant than previously thought, potentially surpassing that of glutathione in certain contexts.