ArticleThe Journal of biological chemistry2009
Cell surface biliverdin reductase mediates biliverdin-induced anti-inflammatory effects via phosphatidylinositol 3-kinase and Akt.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 112 citations in OpenAlex.
- Bilirubin and the Yellow Players in Ferroptosis: A Delicate Balance in Human Health and Disease, with a Focus on the Liver, Cardiovascular System, and Brain.Biomolecules · 2026Review
- 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
- A metabolite-based resistance mechanism against malaria.Science (New York, N.Y.) · 2025Article
- Article
- An Alternative to Biliverdin, Mesobiliverdin IXα and Mesobiliverdin-Enriched Microalgae: A Review on the Production and Applications of Mesobiliverdin-Related Products.Molecules (Basel, Switzerland) · 2025Review
- The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Bilirubin metabolism in relation to cancer.Frontiers in oncology · 2025Review
- Cytoskeleton Remodeling-Related Proteins Represent a Specific Salivary Signature in PSC Patients.Molecules (Basel, Switzerland) · 2024Article
- C-Phycoerythrin Prevents Chronic Kidney Disease-Induced Systemic Arterial Hypertension, Avoiding Oxidative Stress and Vascular Dysfunction in Remanent Functional Kidney.Marine drugs · 2024Article
- Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology.Frontiers in immunology · 2024Review
- Non-invasive assessment of liver fibrosis by serum metabolites in non-human primates and human patients.iScience · 2023Article
- Modulation of Nrf2/HO-1 by Natural Compounds in Lung Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- The gut microbiome and metabolites are altered and interrelated in patients with functional constipation.Frontiers in microbiology · 2023Article
- Heme oxygenase-1 mitigates liver injury and fibrosis via modulation of LNX1/Notch1 pathway in myeloid cells.iScience · 2022Article
- Role of Biliverdin Reductase A in the Regulation of Insulin Signaling in Metabolic and Neurodegenerative Diseases: An Update.International journal of molecular sciences · 2022Review
- Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling.Science signaling · 2022Article
- Reactive Oxygen Species (ROS) and Antioxidants as Immunomodulators in Exercise: Implications for Heme Oxygenase and Bilirubin.Antioxidants (Basel, Switzerland) · 2022Review
- The Bioactivities of Phycocyanobilin from Spirulina.Journal of immunology research · 2022Review
- HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth.Cells · 2021Review
- Endometriosis Is Associated with Functional Polymorphism in the Promoter of Heme Oxygenase 1 (Cells · 2021Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Biliverdin reductase A (BVR) catalyzes the reduction of biliverdin (BV) to bilirubin (BR) in all cells. Others and we have shown that biliverdin is a potent anti-inflammatory molecule, however, the mechanism by which BV exerts its protective effects is unclear. We describe and elucidate a novel finding demonstrating that BVR is expressed on the external plasma membrane of macrophages (and other cells) where it quickly converts BV to BR. The enzymatic conversion of BV to BR on the surface by BVR initiates a signaling cascade through tyrosine phosphorylation of BVR on the cytoplasmic tail. Phosphorylated BVR in turn binds to the p85alpha subunit of phosphatidylinositol 3-kinase and activates downstream signaling to Akt. Using bacterial endotoxin (lipopolysaccharide) to initiate an inflammatory response in macrophages, we find a rapid increase in BVR surface expression. One of the mechanisms by which BV mediates its protective effects in response to lipopolysaccharide is through enhanced production of interleukin-10 (IL-10) the prototypical anti-inflammatory cytokine. IL-10 regulation is dependent in part on the activation of Akt. The effects of BV on IL-10 expression are lost with blockade of Akt. Inhibition of surface BVR with RNA interference attenuates BV-induced Akt signaling and IL-10 expression and in vivo negates the cytoprotective effects of BV in models of shock and acute hepatitis. Collectively, our findings elucidate a potentially important new molecular mechanism by which BV, through the enzymatic activity and phosphorylation of surface BVR (BVR)(surf) modulates the inflammatory response.
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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.