Pleiotropic functions of biliverdin reductase: cellular signaling and generation of cytoprotective and cytotoxic bilirubin

Kapitulnik, Jaime; Maines, Mahin D.

doi:10.1016/j.tips.2008.12.003

Cited by 157 publications

(202 citation statements)

References 71 publications

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“…The role of BR as a beneficial compound with potent antioxidant and anti-inflammatory effects has only been appreciated in recent years [42,43]. Protection against experimental inflammation via HO-1-derived biliverdin has been shown in animal models of proinflammatory cardiovascular [30] and gastrointestinal disorders [44].…”

mentioning

confidence: 99%

Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential

Paine

Eiz‐Vesper

Blasczyk

et al. 2010

Biochemical Pharmacology

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confidence: 99%

Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential

Paine

Eiz‐Vesper

Blasczyk

et al. 2010

Biochemical Pharmacology

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“…In addition to its role in cell growth and apoptotic processes, PKC␦ has been implicated in regulation of membrane ion channels, activation of transcriptional factors, antigen presentation, and with various cancers (3). hBVR, 2 a Ser/Thr/Tyr kinase and a reductase, is a 296-residue soluble polypeptide with an extensive range of input into signal transduction pathways, as well as being a key component of cellular defense mechanisms (4); the reductase activity of hBVR is directly associated with its phosphorylation state (5,6). Depending on the type of stimulus and cell type, activation of PKC␦ and hBVR can exert opposing effects on apoptotic events or bring about a similar outcome on cell survival.…”

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confidence: 99%

“…Because PKC␦ and hBVR both have a broad range of biological activities, their interaction could influence an array of processes that are associated with normal cellular activities, as well as those that are associated with pathophysiology of the cell (1,2,4,39,40). Accordingly, it is reasonable to postulate that the activation of either enzyme has a bearing on the other.…”

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confidence: 99%

The Human Biliverdin Reductase-based Peptide Fragments and Biliverdin Regulate Protein Kinase Cδ Activity

Miralem

Lerner-Marmarosh

Gibbs

et al. 2012

Journal of Biological Chemistry

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Background: hBVR reduces biliverdin to antioxidant bilirubin. PKC␦ promotes tumorigenesis and apoptosis. Results: Complex formation between PKC␦ and hBVR results in transactivation. hBVR-based peptides are identified as substrates or inhibitors of the PKC in vitro and in the cell. Biliverdin inhibits PKC␦. Conclusion: A regulatory loop links PKC␦ and hBVR in cell signaling. Significance: hBVR-based peptides can be used to regulate PKC␦ signaling.

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“…H eme oxygenases (HOs) catalyze the conversion of the prooxidant molecule heme into equimolar amounts of iron, carbon monoxide, and biliverdin (1-3), which is converted into bilirubin in a coupled reaction (4). HO-1, the inducible isoform of HO, is upregulated by a large variety of oxidative stress stimuli and provides antioxidant cytoprotective effects (5,6).…”

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confidence: 99%

Bruton’s Tyrosine Kinase Is Required for TLR-Dependent Heme Oxygenase-1 Gene Activation via Nrf2 in Macrophages

Vijayan

Baumgart-Vogt

Naidu

et al. 2011

The Journal of Immunology

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Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of heme degradation and provides cytoprotection against oxidative stress by its products carbon monoxide and biliverdin. More recently, HO-1 has also been shown to exert immunomodulatory functions via cell type-specific anti-inflammatory effects in myeloid/macrophage cells. In the current study, it is demonstrated that Bruton's tyrosine kinase (Btk), the gene of which is mutated in the human immunodeficiency X-linked agammaglobulinemia, is involved in the upregulation of HO-1 gene expression via TLR signaling in macrophages. The specific Btk inhibitor LFM-A13 blocked HO-1 induction by the classical TLR4 ligand LPS in cell cultures of RAW264.7 monocytic cells and primary mouse alveolar macrophages. Moreover, upregulation of HO-1 gene expression was abrogated in LPS-stimulated alveolar macrophages from Btk−/− mice. Transfection studies with luciferase reporter gene constructs demonstrated that LPS-dependent induction of HO-1 promoter activity was attenuated by pharmacological Btk inhibition and by an overexpressed dominant-negative mutant of Btk. This induction was mediated by the transcription factor Nrf2, which is a master regulator of the antioxidant cellular defense. Accordingly, nuclear translocation of Nrf2 in LPS-treated macrophages was reduced by Btk inhibition. The generation of reactive oxygen species, but not that of NO, was involved in this regulatory pathway. Btk-dependent induction of HO-1 gene expression was also observed upon macrophage stimulation with ligands of TLR2, TLR6, TLR7, and TLR9, suggesting that Btk is required for HO-1 gene activation by major TLR pathways.

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Pleiotropic functions of biliverdin reductase: cellular signaling and generation of cytoprotective and cytotoxic bilirubin

Cited by 157 publications

References 71 publications

Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential

Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential

The Human Biliverdin Reductase-based Peptide Fragments and Biliverdin Regulate Protein Kinase Cδ Activity

Bruton’s Tyrosine Kinase Is Required for TLR-Dependent Heme Oxygenase-1 Gene Activation via Nrf2 in Macrophages

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