The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Bilirubin and glutathione have complementary antioxidant and cytoprotective roles
Open accessAbstract
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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Cites
Free Radicals in Biology and Medicine
Halliwell, B., & Gutteridge, J. M. C. (2015) · doi:10.1093/acprof:oso/9780198717478.001.0001 · Cited by 8,990
Antioxidant treatment for amyotrophic lateral sclerosis or motor neuron disease
Orrell, R. W., Lane, R. J., & Ross, M. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002829.pub4 · Cited by 98
Cited by
Mechanisms of Cell Protection by Heme Oxygenase-1
Gozzelino, R., Jeney, V., & Soares, M. P. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105600 · Cited by 1,241
Regulation of inflammation by the antioxidant haem oxygenase 1
Campbell, N. K., Fitzgerald, H. K., & Dunne, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00491-x · Cited by 420
Biochemical basis and metabolic interplay of redox regulation
Zhang, L., Wang, X., Cueto, R., Effi, C., Zhang, Y., Tan, H., Qin, X., Ji, Y., Yang, X., & Wang, H. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101284 · Cited by 308
The unusual amino acid L-ergothioneine is a physiologic cytoprotectant
Paul, B. D., & Snyder, S. H. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.163 · Cited by 304
Self-citationCoupling Heme and Iron Metabolism via Ferritin H Chain
Gozzelino, R., & Soares, M. P. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5666 · Cited by 151
Metadata
- Authors
- Sedlak, T. W., Saleh, M., Higginson, D. S., Paul, B. D., Juluri, K. R., & Snyder, S. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-31
- Volume
- 106
- Issue
- 13
- Pages
- 5171-5176
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2170928666
- Cited by
- 530
- References
- 2
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Sedlak, T. W., Saleh, M., Higginson, D. S., Paul, B. D., Juluri, K. R., & Snyder, S. H. (2009). Bilirubin and glutathione have complementary antioxidant and cytoprotective roles. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0813132106
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