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June Lee, Karabasappa Mailar, Ok-Kyung Yoo, Won Jun Choi, Young-Sam Keum
Heme oxygenase-1 (HO-1) catalyzes the enzymatic degradation of heme to produce three anti-oxidant molecules: carbon monoxide (CO), ferrous ion (Fe2+ ), and biliverdin. Induction of HO-1 is currently considered as a feasible strategy to treat oxidative stress-related diseases. In the present study, we identified marliolide as a novel inducer of HO-1 in human normal keratinocyte HaCaT cells. Mechanism-based studies demonstrated that the induction of HO-1 by marliolide occurred through activation of NRF2/ARE via direct binding of marliolide to KEAP1...
February 23, 2018: European Journal of Medicinal Chemistry
Madasamy Thangamuthu, Willimann Eric Gabriel, Christian Santschi, Olivier J F Martin
Practice oriented point-of-care diagnostics require easy-to-handle, miniaturized, and low-cost analytical tools. In a novel approach, screen printed carbon electrodes (SPEs), which were functionalized with nanomaterials, are employed for selective measurements of bilirubin, which is an important biomarker for jaundice. Multi-walled carbon nanotubes (MWCNT) and graphene separately deposited on SPEs provide the core of an electrochemical sensor for bilirubin. The electrocatalytic activity towards bilirubin oxidation (bilirubin to biliverdin) was observed at +0...
March 7, 2018: Sensors
Zongdong Li, Natasha M Nesbitt, Lisa E Malone, Dimitri V Gnatenko, Song Wu, Daifeng Wang, Wei Zhu, Geoffrey D Girnun, Wadie F Bahou
Bioenergetic requirements of hematopoietic stem cells (HSC) and pluripotent stem cells (PSC) vary with lineage fate, and cellular adaptations rely largely on substrate (glucose/glutamine) availability and mitochondrial function to balance TCA-derived anabolic and redox-regulated antioxidant functions.  Heme synthesis and degradation converge in a linear pathway that utilizes TCA cycle-derived carbon in cataplerotic reactions of tetrapyrrole biosynthesis, terminated by NAD(P)H-dependent biliverdin reductases (IXα, BLVRA and IXβ, BLVRB) that lead to bilirubin generation and cellular antioxidant functions...
March 2, 2018: Biochemical Journal
Lauren Weaver, Abdul-Rizaq Ali Hamoud, David E Stec, Terry D Hinds
The buildup of fat in the liver (hepatic steatosis) is the first step in a series of incidents that may drive hepatic disease. Obesity is the leading cause of nonalcoholic fatty liver disease (NAFLD) in which hepatic steatosis progresses to liver disease. Chronic alcohol exposure also induces fat accumulation in the liver and shares numerous similarities to obesity-induced NAFLD. Regardless, if hepatic steatosis is due to obesity or long-term alcohol use, it still may lead to hepatic fibrosis, cirrhosis, or possibly hepatocellular carcinoma...
March 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Natasha M Nesbitt, Xiliang Zheng, Zongdong Li, José A Manso, Wan-Yi Yen, Lisa E Malone, Jorge Ripoll-Rozada, Pedro José Barbosa Pereira, Timothy J Mantle, Jin Wang, Wadie F Bahou
Heme cytotoxicity is minimized by a two-step catabolic reaction that generates biliverdin (BV) and bilirubin (BR) tetrapyrroles. The second step is regulated by two non-redundant biliverdin reductases (IXα[BLVRA] and IXβ [BLVRB]), which retain isomeric specificity and NAD(P)H-dependent redox coupling linked to BR's antioxidant function.  Defective BLVRB enzymatic activity with antioxidant mishandling has been implicated in metabolic consequences of hematopoietic lineage fate and enhanced platelet counts in humans...
February 27, 2018: Journal of Biological Chemistry
Vijith Vijayan, Frank A D T G Wagener, Stephan Immenschuh
Heme oxygenase (HO)-1, the inducible isoform of the heme-degrading enzyme HO, plays a critical role in inflammation and iron homeostasis. Regulatory functions of HO-1 are mediated via the catalytic breakdown of heme, which is an iron-containing tetrapyrrole complex with potential pro-oxidant and pro-inflammatory effects. The HO reaction produces the antioxidant and anti-inflammatory compounds carbon monoxide (CO) and biliverdin, subsequently converted into bilirubin, along with iron, which is reutilized for erythropoiesis...
February 13, 2018: Biochemical Pharmacology
Melissa P Homsher, Michael T Astor, Justin K Hines, Michael W Butler
Most antioxidants have multiple functions; in addition to minimizing oxidative damage, many antioxidants have immune-modulating properties. For example, biliverdin is produced in the liver and spleen from the breakdown of heme, and has putative immune-suppressing and antioxidant properties. However, the majority of these properties have been investigated in vitro or in mammalian models, in which biliverdin reductase converts virtually all biliverdin to bilirubin. Thus, biliverdin's physiological roles remain largely untested...
January 29, 2018: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Samuel O Adeosun, Kyle H Moore, David M Lang, Assumpta C Nwaneri, Terry D Hinds, David E Stec
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...
2018: Reactive Oxygen Species (Apex, N.C.)
Hellíada Vasconcelos Chaves, Danielle Rocha do Val, Kátia Alves Ribeiro, Jonas Cavalcante Lemos, Ricardo Basto Souza, Francisco Isaac Fernandes Gomes, Rodrigo Maranguape Silva da Cunha, Vicente de Paulo Teixeira Pinto, Gerardo Cristino Filho, Marcellus Henrique Loiola Ponte de Souza, Mirna Marques Bezerra, Gerly Anne de Castro Brito
OBJECTIVE AND DESIGN: To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats. MATERIALS AND METHODS: Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1β mRNA time course expression and immunohistochemical analyses...
January 23, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Yi-Tai Chou, Fu-Fei Hsu, Dun-Yao Hu, Ying-Chih Chen, Yuan-Hao Hsu, John T-A Hsu, Lee-Young Chau
BACKGROUND: Heme oxygenase (HO) catalyzes NADPH-dependent degradation of heme to liberate iron, carbon monoxide and biliverdin. The interaction between HO and cytochrome P450 reductase (CPR), an electron donor, is essential for HO activity. HO-1 is a stress-inducible isoform whereas HO-2 is constitutively expressed. HO-1 induction is commonly seen in cancers and impacts disease progression, supporting the possibility of targeting HO-1 for cancer therapy. METHODS: We employed a cell-based bioluminescence resonance energy transfer assay to screen compounds with ability to inhibit HO-1/CPR interaction...
January 23, 2018: Journal of Biomedical Science
Katarzyna Magierowska, Tomasz Brzozowski, Marcin Magierowski
Heme oxygenase (HO) catalyzes the degradation of toxic free heme to the equimolar amounts of biliverdin, Fe2+ and concurrently releases of carbon monoxide (CO). CO is nowadays increasingly recognized as an important signaling molecule throughout the body that is involved in many physiological processes and shows multidirectional biological activity. Recent evidence indicates that CO exhibits the anti-inflammatory, anti-proliferative, anti-apoptotic, anti-aggregatory and vasodilatory properties. The cellular mechanisms underlying the activity of CO involve stimulation of cGMP-dependent signaling pathway and large conductance calcium activated K+ channels, the activation of mitogen-activated protein kinases and the nuclear factor k-light chain-enhancer of activated B cells transcription factor pathway...
January 29, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Andrew J Ghio, Martin Case, Joleen M Soukup
Heme oxygenase (HO) is an essential, rate-limiting protein which catalyzes the breakdown of heme to iron, carbon monoxide (CO), and biliverdin. The alpha methene bridge of the heme is eliminated as CO which can be measured as blood carboxyhemoglobin (COHb). Using blood concentrations of COHb as a measure reflecting HO activity, we tested the postulate that the activity of HO changes with exercise. Ten healthy, nonsmoking volunteers (5 females and 5 males with a mean age ± standard deviation of 25.7 ± 3...
January 17, 2018: Free Radical Research
Ta-Lun Kao, Yao-Li Chen, Yu-Ping Kuan, Wei-Chun Chang, Yu-Chen Ho, Shuyuan Yeh, Long-Bin Jeng, Wen-Lung Ma
BACKGROUND: After living donor liver transplantation (LDLT), rising serum bilirubin levels commonly indicate insufficient numbers of hepatocytes are available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450 (CYP) 2A6 in humans (or cyp2a4 in rodents) can function as "bilirubin oxidase." Functional hepatocytes contain abundant CYP2A6, which is considered a marker for hepatocyte function recovery...
November 2017: Cell Transplantation
Anna Maria Spanaki, Theonymfi Tavladaki, Helen Dimitriou, Andrey V Kozlov, J Catharina Duvigneau, Eftychia Meleti, Adelheid Weidinger, Evangelos Papakonstantinou, George Briassoulis
BACKGROUND: Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. METHODS: Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX...
January 16, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
Luc Rochette, Marianne Zeller, Yves Cottin, Catherine Vergely
In patients with diabetes, the hyperglycemia-driven excess generation of reactive oxygen species (ROS) induces oxidative stress (OS) in a variety of tissues. OS is closely associated with chronic inflammation and has a key role in the pathogenesis of vascular complications. The enzymes that generate ROS and gasotransmitters are redox regulated and are implicated in cellular signaling. As a result of cellular metabolism, cells produce significant amounts of carbon monoxide (CO), mainly from heme degradation catalyzed by heme oxygenases (HOs)...
December 14, 2017: Trends in Endocrinology and Metabolism: TEM
Lovely Mahawar, Gyan Singh Shekhawat
Haem oxygenase (HO) is a universal enzyme that catalyses stereospecific cleavage of haem to BV IX α and liberates Fe+2 ion and CO as by-product. Beside haem degradation, it has important functions in plants that include cellular defence, stomatal regulation, iron mobilization, phytochrome chromophore synthesis, and lateral root formation. Phytochromes are an extended family of photoreceptors with a molecular mass of 250 kDa and occur as a dimer made up of 2 equivalent subunits of 125 kDa each. Each subunit is made of two components: the chromophore, a light-capturing pigment molecule and the apoprotein...
March 2018: Plant, Cell & Environment
Weiyu Chen, Ghassan J Maghzal, Anita Ayer, Cacang Suarna, Louise L Dunn, Roland Stocker
Bilirubin, a byproduct of heme catabolism, has been shown to be an effective lipid-soluble antioxidant in vitro. Bilirubin is able to inhibit free radical chain reactions and protects against oxidant-induced damage in vitro and ex vivo. However, direct evidence for bilirubin's antioxidant effects in vivo remains limited. As bilirubin is formed from biliverdin by biliverdin reductase, we generated global biliverdin reductase-a gene knockout (Bvra-/- ) mice to assess the contribution of bilirubin as an endogenous antioxidant...
February 1, 2018: Free Radical Biology & Medicine
Francisco J Ibáñez, Mónica A Farías, Angello Retamal-Díaz, Janyra A Espinoza, Alexis M Kalergis, Pablo A González
Heme oxygenase-1 (HO-1) is an inducible enzyme that is expressed in response to physical and chemical stresses, such as ultraviolet radiation, hyperthermia, hypoxia, reactive oxygen species (ROS), as well as cytokines, among others. Its activity can be positively modulated by cobalt protoporphyrin (CoPP) and negatively by tin protoporphirin (SnPP). Once induced, HO-1 degrades iron-containing heme into ferrous iron (Fe2+ ), carbon monoxide (CO) and biliverdin. Importantly, numerous products of HO-1 are cytoprotective with anti-apoptotic, anti-oxidant, anti-inflammatory, and anti-cancer effects...
2017: Frontiers in Microbiology
Benjamin Ledermann, Meike Schwan, Johannes A Sommerkamp, Eckhard Hofmann, Oded Béjà, Nicole Frankenberg-Dinkel
Ferredoxin-dependent bilin reductases (FDBRs) are a class of enzymes reducing the heme metabolite biliverdin IXα (BV) to form open-chain tetrapyrroles used for light-perception and light-harvesting in photosynthetic organisms. Thus far, seven FDBR families have been identified, each catalysing a distinct reaction and either transferring two or four electrons from ferredoxin onto the substrate. The newest addition to the family is PcyX, originally identified from metagenomics data derived from phage. Phylogenetically, PcyA is the closest relative catalysing the reduction of BV to phycocyanobilin...
January 2018: FEBS Journal
Duane T Lowe
BACKGROUND: Cupping therapy is a traditional therapy that has been employed worldwide for thousands of years. Despite a lack of quality clinical studies evaluating the efficacy of cupping therapy, its long history and widespread use throughout the world suggests the commonly claimed health benefits should not be completely discounted as without merit. PURPOSE: The goal of this paper is to present the research detailing what is known concerning the effects of suction on skin and underlying tissue, and the reaction of the body to that stimulus...
November 2017: Complementary Therapies in Clinical Practice
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