Biliverdin reductase isozymes in metabolism

O’Brien, Luke; Hosick, Peter A.; John, Kezia; Stec, David E.; Hinds, Terry D.

doi:10.1016/j.tem.2015.02.001

Cited by 113 publications

(115 citation statements)

References 77 publications

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“…Bilirubin increased tolerance to islet allograft by both its anti-inflammatory and anti-oxidative properties 62,63 . Additionally, biliverdin reductase acts as transcriptional factor and increases HO-1/HO-2 levels and HO activity 26 and protects against glucose intolerance (reviewed in 64 ) through a mechanism involving activation of phosphatidylinositol 3-kinase (P13K) 65 . Unconjugated bilirubin mediated HO-1-induced vascular benefit in diabetes 66 and administration of mesobiliverdin analogues of biliverdin to the pancreas lowered blood glucose and increased insulin function 67 .…”

Section: Biological Action Of Bilirubin/biliverdinmentioning

confidence: 99%

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Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome

Abraham

Junge

Drummond

2016

Trends in Pharmacological Sciences

118

129

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The global epidemic of obesity continues unabated with sequelae of diabetes and metabolic syndrome. This review reflects the dramatic increase in research on the role of increased expression of heme oxygenase (HO)-1/HO-2, biliverdin reductase, and HO activity on vascular disease. The HO system engages with other systems to mitigate the deleterious effects of oxidative stress in obesity and cardiovascular disease (CVD). Recent reports indicate that HO-1/HO-2 protein expression and HO activity have several important roles in hemostasis and ROS-dependent perturbations associated with metabolic syndrome. HO-1 protects tissue during inflammatory stress in obesity through the degradation of pro-oxidant heme and the production of carbon monoxide (CO) and bilirubin, both of which have anti-inflammatory and anti-apoptotic properties. In contrast, repression of HO-1 is associated with increases of cellular heme and inflammatory conditions including hypertension, stroke and atherosclerosis. HO-1 is a major focus in the development of potential therapeutic strategies to reverse the clinical complications of obesity and metabolic syndrome.

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Section: Biological Action Of Bilirubin/biliverdinmentioning

confidence: 99%

“…Additional studies have demonstrated that both free and albumin-bound bilirubin can inhibit the oxidation of low density lipoproteins (LDL) 73 . The roles of bilirubin and biliverdin reductase in obesity and CVD have been recently reviewed 64,72 .…”

Section: Biological Action Of Bilirubin/biliverdinmentioning

confidence: 99%

Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome

Abraham

Junge

Drummond

2016

Trends in Pharmacological Sciences

118

129

View full text Add to dashboard Cite

show abstract

“…Another interesting protein significantly increased in abundance is BLVRB, a flavin reductase, which converts biliverdin IXβ to bilirubin Ixβ and the latter in turn increases insulin sensitivity (O’Brien et al, 2015) as probable defense mechanisms against the ensuing insulin resistance. The increase in the BLBVRB protein in the MUHO group has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

A Proteomics Based Approach Reveals Differential Regulation of Visceral Adipose Tissue Proteins between Metabolically Healthy and Unhealthy Obese Patients

Alfadda

Masood

Al-Naami

et al. 2017

Molecules and Cells

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Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood.In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese patients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation. Two dimensional difference in-gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was carried out. A total of 28 proteins were identified with a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p ≤ 0.05) between the groups. 11 proteins showed increased abundance while 17 proteins were decreased in the metabolically unhealthy obese compared to the healthy obese. The differentially expressed proteins belonged broadly to three functional categories: (i) protein and lipid metabolism (ii) cytoskeleton and (iii) regulation of other metabolic processes. Network analysis by Ingenuity pathway analysis identified the NFκB, IRK/MAPK and PKC as the nodes with the highest connections within the connectivity map. The top network pathway identified in our protein data set related to cellular movement, hematological system development and function, and immune cell trafficking. The VAT proteome between the two groups differed substantially between the groups which could potentially be the reason for metabolic dysfunction.

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“…Heme oxygenase (HO) is a critical component of a major antioxidant pathway by the generation of bilirubin (1, 12). Initially, HO breaks down heme to biliverdin, free iron, and carbon monoxide (CO), and biliverdin is then reduced to bilirubin by the enzyme biliverdin reductase (BVR) (1, 12).…”

Section: Introduction and Methods Principlementioning

confidence: 99%

“…Initially, HO breaks down heme to biliverdin, free iron, and carbon monoxide (CO), and biliverdin is then reduced to bilirubin by the enzyme biliverdin reductase (BVR) (1, 12). In adults, this reaction is catalyzed by the A isoform of BVR (BVRA).…”

Section: Introduction and Methods Principlementioning

confidence: 99%

A Novel Fluorescence-Based Assay for the Measurement of Biliverdin Reductase Activity

Adeosun

Moore

Lang

et al. 2018

ROS

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Biliverdin reductase (BVR) is the enzyme responsible for the last step in the production of bilirubin from the breakdown of heme. Bilirubin is one of the most potent antioxidant molecules in the body. Monitoring BVR activity is essential in studying the antioxidant capacity of cells and tissues. Traditional methods of determining BVR activity have relied on the measurement of bilirubin converted from biliverdin using absorbance spectroscopy. The approach has limited sensitivity and requires large quantities of cells or tissues. We have developed a novel fluorescence-based method utilizing the eel protein, UnaG, for the detection of bilirubin produced by BVR. The UnaG protein only fluoresces by the induction of bilirubin. We have also used this approach to measure intracellular bilirubin content of cultured cells. We validated this assay using cell lysates from mouse liver and immortalized murine hepatic cell line (Hepa1c1c7) and kidney cell line (MCT) in which BVR isoform A (BVRA) was either knocked out via CRISPR or stably overexpressed by lentivirus. Also, we tested the method using previously reported putative BVRA inhibitors, Closantel and Ebselen. These studies show a new method for measuring bilirubin intracellularly and in lysates.

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Biliverdin reductase isozymes in metabolism

Cited by 113 publications

References 77 publications

Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome

Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome

A Proteomics Based Approach Reveals Differential Regulation of Visceral Adipose Tissue Proteins between Metabolically Healthy and Unhealthy Obese Patients

A Novel Fluorescence-Based Assay for the Measurement of Biliverdin Reductase Activity

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