The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury
Open accessAbstract
Heme oxygenase (HO) catalyzes the conversion of heme to carbon monoxide, iron, and biliverdin, which is immediately reduced to bilirubin (BR). Two HO active isozymes exist: HO1, an inducible heat shock protein, and HO2, which is constitutive and highly concentrated in neurons. We demonstrate a neuroprotective role for BR formed from HO2. Neurotoxicity elicited by hydrogen peroxide in hippocampal and cortical neuronal cultures is prevented by the phorbol ester, phorbol 12-myristate 13-acetate (PMA) via stimulation of protein kinase C. We observe phosphorylation of HO2 through the protein kinase C pathway with enhancement of HO2 catalytic activity and accumulation of BR in neuronal cultures. The neuroprotective effects of PMA are prevented by the HO inhibitor tin protoporphyrin IX and in cultures from mice with deletion of HO2 gene. Moreover, BR, an antioxidant, is neuroprotective at nanomolar concentrations.
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Cites
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Self-citationReduced stress defense in heme oxygenase 1-deficient cells
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Molecular cloning and expression of a receptor for human tumor necrosis factor
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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
Pro-oxidant and cytotoxic effects of circulating heme
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The unusual amino acid L-ergothioneine is a physiologic cytoprotectant
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Self-citationHeme oxygenase-1 and neurodegeneration: expanding frontiers of engagement
Schipper, H. M., Song, W., Zukor, H., Hascalovici, J. R., & Zeligman, D. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06160.x · Cited by 298
Metadata
- Authors
- Doré, S., Takahashi, M., Ferris, C. D., Hester, L. D., Guastella, D., & Snyder, S. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-03-02
- Volume
- 96
- Issue
- 5
- Pages
- 2445-2450
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2030365747
- Cited by
- 699
- References
- 40
- FWCI
- 12.61
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. https://app.cochat.ai/papers/10.1073/pnas.96.5.2445
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- Doré, S., Takahashi, M., Ferris, C. D., Hester, L. D., Guastella, D., & Snyder, S. H. (1999). Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.5.2445
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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