Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury

Kim, Jin Yong; Lee, Dong Yun; Kang, Sukmo; Miao, Wenjun; Kim, Hyungjun; Lee, Yonghyun; Jon, Sangyong

doi:10.1016/j.biomaterials.2017.04.011

Cited by 109 publications

(83 citation statements)

References 31 publications

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“…Moreover, intraperitoneal administration of bilirubin has been shown to prevent cardiolipin oxidation and to reduce the infarct size in a rat model of coronary ischemia/reperfusion injury (Ben-Amotz et al, 2014). More recently, preconditioning performed using nanoparticles of pegylated bilirubin was highly effective in preventing hepatic ischemic damage (Kim et al, 2017). Furthermore, the critical importance of the endogenous HMOX1/bilirubin pathway has been demonstrated following supplementation cell culture media not only with UCB but also with hemin.…”

Section: Bilirubin and Ischemia/reperfusion Injurymentioning

confidence: 99%

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

2020

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Among antioxidants in the human body, bilirubin has been recognized over the past 20 years to afford protection against different chronic conditions, including inflammation and cardiovascular disease. Moderate increases in plasma concentration and cellular bilirubin generation from metabolism of heme via heme oxygenase (HMOX) in virtually all tissues can modulate endothelial and vascular function and exert antioxidant and antiinflammatory roles. This review aims to provide an up-to-date and critical overview of the molecular mechanisms by which bilirubin derived from plasma or from HMOX1 activation in vascular cells affects endothelial function. Understanding the molecular actions of bilirubin may critically improve the management not only of key cardiovascular diseases, but also provide insights into a broad spectrum of pathologies driven by endothelial dysfunction. In this context, therapeutic interventions aimed at mildly increasing serum bilirubin as well as bilirubin generated endogenously by endothelial HMOX1 should be considered.

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Section: Bilirubin and Ischemia/reperfusion Injurymentioning

confidence: 99%

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

2020

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“…In adults, this reaction is catalyzed by the A isoform of BVR (BVRA). Bilirubin is one of the most potent antioxidant molecules in the body (15, 16), and has been demonstrated to play protective roles against a wide range of diseases and pathologic conditions including ischemia reperfusion-injury, fatty liver disease, obesity, and diabetes (2, 3, 5–7, 9, 11, 13). Recently, bilirubin has been shown to bind to the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα), which is the only function known outside of its antioxidant properties (13).…”

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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“…Hepatic IRI was induced following a common protocol that was described previously [15,16]. To generate a mouse hepatic IRI model, a microvascular clamp was applied to the Glisson system.…”

Section: Induction Of the Hepatic Iri Models In Mice And Cellsmentioning

confidence: 99%

lncRNA AK054386 Functions as a ceRNA to Sequester miR-199 and Induce Sustained Endoplasmic Reticulum Stress in Hepatic Reperfusion Injury

Dai

Qiao

Zhang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Hepatic ischemia-reperfusion injury (IRI) is a very complex pathological process that is often associated with liver trauma and surgery, especially liver transplantation surgery. Although endoplasmic reticulum stress (ERS) plays a role in this process, the posttranscriptional regulators and the underlying mechanisms are still unclear. Here, we report that the lncRNA AK054386 was increased in hepatic IRI models. Furthermore, AK054386 can act as a “competing endogenous RNA (ceRNA)” and regulate ERS-related factors by binding and sequestering miR-199, which was shown to inhibit ERS in our previous report. Increased expression of AK054386, which might be mediated by activated NF-κB, resulted in sustained ERS and increased cell apoptosis and death in hepatic IRI mouse and cellular models. In contrast, AK054386 inhibition had protective effects on these models. Our data indicate that AK054386 and miR-199 are critical players in hepatic IRI, and we broadened the scope regarding ceRNA mechanisms. We hope that our results will improve the understanding of hepatic IRI and may provide potential therapeutic targets.

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Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury

Cited by 109 publications

References 31 publications

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?

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

lncRNA AK054386 Functions as a ceRNA to Sequester miR-199 and Induce Sustained Endoplasmic Reticulum Stress in Hepatic Reperfusion Injury

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