ArticleProceedings of the National Academy of Sciences of the United States of America1999
Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 206 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
206 citing papers in PubMed, 701 citations in OpenAlex.
- Bilirubin in Parkinson's disease: pathogenic mechanisms and therapeutic potentials.Frontiers in neuroscience · 2026Review
- The Heme Oxygenase/Biliverdin Reductase System as a Therapeutic Target to Counteract Cellular Senescence in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Hepatic function is associated with cognitive function in patients with stable schizophrenia.BMC psychiatry · 2025Article
- Biliverdin reductase A is a major determinant of protective NRF2 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Betulinic Acid-EnrichedAntioxidants (Basel, Switzerland) · 2025Article
- Antioxidant Molecules in the Human Vitreous Body During Prenatal Eye Development.Antioxidants (Basel, Switzerland) · 2025Review
- The diagnostic potential of unconjugated bilirubin in schizophrenia and bipolar disorder.BMC psychiatry · 2025Article
- Hemin-induced transient senescence via DNA damage response: a neuroprotective mechanism against ferroptosis in intracerebral hemorrhage.Communications biology · 2025Article
- Iron Overload, Microbleeding and the Role of Bilirubin in Alzheimer's Disease Brain: Revisiting the Vascular Hypothesis.International journal of molecular sciences · 2025Review
- Bilirubinemia and retinopathy of prematurity in infants ≤ 29 weeks' gestational age.Pediatric research · 2025Article
- Aging and MPTP Sensitivity Depend on Molecular and Ultrastructural Signatures of Astroglia and Microglia in Mice Substantia Nigra.Cellular and molecular neurobiology · 2025Article
- Association of total bilirubin and prognosis in disorders of consciousness.Scientific reports · 2024Article
- Article
- Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury.Communications biology · 2024Article
- Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition.ACS chemical neuroscience · 2024Review
- Loss of Biliverdin Reductase Increases Oxidative Stress in the CyanobacteriumMicroorganisms · 2023Article
- Article
- The effects of Korean Red Ginseng on heme oxygenase-1 with a focus on mitochondrial function in pathophysiologic conditions.Journal of ginseng research · 2023Review
- Endogenous and Exogenous Antioxidants as Agents Preventing the Negative Effects of Contrast Media (Contrast-Induced Nephropathy).Pharmaceuticals (Basel, Switzerland) · 2023Review
- Heme Interactions as Regulators of the Alternative Pathway Complement Responses and Implications for Heme-Associated Pathologies.Current issues in molecular biology · 2023Review
146 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
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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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.