ArticleCell death & disease2015
Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Integrated machine learning identifies biomarkers for bilirubin-induced Alzheimer's disease-like lesions in neonates and adults.Scientific reports · 2025Article
- Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.World journal of gastroenterology · 2024Article
- Expression profiling of N6-methyladenosine-modified mRNA in PC12 cells in response to unconjugated bilirubin.Molecular biology reports · 2023Article
- Models of bilirubin neurological damage: lessons learned and new challenges.Pediatric research · 2023Review
- Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage.Neuron · 2023Article
- Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis.Frontiers in pharmacology · 2023Review
- Ameliorative effect of oregano (Origanum vulgare) versus silymarin in experimentally induced hepatic encephalopathy.Scientific reports · 2022Article
- Bilirubin-Induced Neurological Damage: Current and Emerging iPSC-Derived Brain Organoid Models.Cells · 2022Review
- Hyperbilirubinemia after surgical repair for acute type a aortic dissection: A propensity score-matched analysis.Frontiers in physiology · 2022Article
- Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy.Frontiers in medicine · 2021Article
- Quantitative proteomic characterization of microvesicles/exosomes from the cerebrospinal fluid of patients with acute bilirubin encephalopathy.Molecular medicine reports · 2020Article
- Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity.Brain research bulletin · 2020Article
- Experimental models assessing bilirubin neurotoxicity.Pediatric research · 2020Review
- Mouse models and strain-dependency of Chédiak-Higashi syndrome-associated neurologic dysfunction.Scientific reports · 2019Article
- High unbound bilirubin for age: a neurotoxin with major effects on the developing brain.Pediatric research · 2019Review
- Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat.Scientific reports · 2018Article
- Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells.Oxidative medicine and cellular longevity · 2018Article
- Reverse chemical ecology: Olfactory proteins from the giant panda and their interactions with putative pheromones and bamboo volatiles.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Repeated AAV-mediated gene transfer by serotype switching enables long-lasting therapeutic levels of hUgt1a1 enzyme in a mouse model of Crigler-Najjar Syndrome Type I.Gene therapy · 2017Article
- Developmental, Genetic, Dietary, and Xenobiotic Influences on Neonatal Hyperbilirubinemia.Molecular pharmacology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration.
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