ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Characterization of the human biliverdin reductase gene structure and regulatory elements: promoter activity is enhanced by hypoxia and suppressed by TNF-alpha-activated NF-kappaB.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Biliverdin reductase A deficiency reveals sex- and brain region-specific vulnerability to high-fat diet feeding.Redox biology · 2026Article
- The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.Clinical science (London, England : 1979) · 2025Review
- Diagnostic Role of Bile Pigment Components in Biliary Tract Cancer.Biomolecules & therapeutics · 2023Article
- Role of Biliverdin Reductase A in the Regulation of Insulin Signaling in Metabolic and Neurodegenerative Diseases: An Update.International journal of molecular sciences · 2022Review
- BVR-A Deficiency Leads to Autophagy Impairment through the Dysregulation of AMPK/mTOR Axis in the Brain-Implications for Neurodegeneration.Antioxidants (Basel, Switzerland) · 2020Article
- Heme-Derived Metabolic Signals Dictate Immune Responses.Frontiers in immunology · 2020Review
- Regenerative Effects of Heme Oxygenase Metabolites on Neuroinflammatory Diseases.International journal of molecular sciences · 2018Review
- Prostate cancer diagnosis and characterization with mass spectrometry imaging.Prostate cancer and prostatic diseases · 2018Review
- Characterization of heme oxygenase and biliverdin reductase gene expression in zebrafish (Danio rerio): Basal expression and response to pro-oxidant exposures.Toxicology and applied pharmacology · 2016Article
- Hypoxia inducible factor-1 mediates the expression of the immune checkpoint HLA-G in glioma cells through hypoxia response element located in exon 2.Oncotarget · 2016Article
- Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Biliverdin reductase: a target for cancer therapy?Frontiers in pharmacology · 2015Review
- Bach1 overexpression in Down syndrome correlates with the alteration of the HO-1/BVR-a system: insights for transition to Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2015Article
- Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.PLoS pathogens · 2013Article
- Go green: the anti-inflammatory effects of biliverdin reductase.Frontiers in pharmacology · 2012Article
- Heme and HO-1 Inhibition of HCV, HBV, and HIV.Frontiers in pharmacology · 2012Article
- Biliverdin reductase: more than a namesake - the reductase, its Peptide fragments, and biliverdin regulate activity of the three classes of protein kinase C.Frontiers in pharmacology · 2012Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
hBVR is a Ser/Thr/Tyr kinase/scaffold protein/transcription factor/intracellular transporter of regulators. hBVR is an upstream activator of the insulin/IGF-1/MAPK/PI3K signaling pathway, and of NF-kappaB. As a reductase, it converts biliverdin to the antioxidant, bilirubin. hBVR gene has 8 exons; exon 1 is not translated. We report the characterization of hBVR promoter and its negative and positive regulation, respectively, by TNF-alpha and hypoxia. The 5' end of exon 1 was defined by primer extension analyses; deletion of an inhibitor sequence 350-425 bp upstream of this exon enhanced the promoter activity. One of two NF-kappaB binding sites in the 836-bp promoter was functional; the P65 subunit of NF-kappaB and TNF-alpha acted as inhibitors. On the basis of EMSA and ChIP assays, TNF-alpha treatment increases binding of NF-kappaB to its regulatory element. Overexpression of IkappaB increased hBVR mRNA. Biliverdin, but not bilirubin, was as effective as TNF-alpha in inhibiting hBVR promoter activity. Only one of 4 hypoxia responsive elements (HREs) bound to HIF-1alpha and ARNT expressed in HEK293A cells. An abasic site was introduced at the 3' G of the HRE. This element bound HIF-1 in the gel shift and in in-cell luciferase assays. hBVR was detected in the nucleus at 1, 2, and 4 h after hypoxia (1% O(2)), at which times its kinase and reductase activities were increased. Because hypoxia positively influences hBVR promoter and phosphorylation and TNF-alpha activated NF-kappaB inhibits the promoter, while biliverdin inhibits both NF-kappaB activity and hBVR promoter, we propose a regulatory mechanism for NF-kappaB by hypoxia and TNF-alpha centered on hBVR/biliverdin.
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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.