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Biliverdin

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https://www.readbyqxmd.com/read/27908781/heme-oxygenase-1-metabolite-biliverdin-not-iron-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication
#1
Angke Zhang, Hong Duan, Na Li, Lijuan Zhao, Fengxing Pu, Baicheng Huang, Chunyan Wu, Yuchen Nan, Taofeng Du, Yang Mu, Qin Zhao, Yani Sun, Gaiping Zhang, Julian A Hiscox, En-Min Zhou, Shuqi Xiao
Porcinereproductiveandrespiratorysyndromevirus (PRRSV) causes significant economic losses to the pork industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) interferes with PRRSV replication. To elucidate the mechanisms involved, here we assess whether the HO-1 downstream metabolites biliverdin (BV) and/or iron mediate the HO-1 antiviral effect. We demonstrate a BV concentration-dependent suppression of PRRSV replication and show that virions are not directly inactivated by BV. Additionally, BV or N-acetyl cysteine (NAC) significantly reduced reactive oxygen species (ROS) in PRRSV-infected MARC-145 cells; however, because NAC did not reduce viral load, the BV antiviral effect is independent of decreased ROS levels...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27906108/heme-oxygenase-and-carbon-monoxide-protect-from-muscle-dystrophy
#2
Mun Chun Chan, Olivia Ziegler, Laura Liu, Glenn C Rowe, Saumya Das, Leo E Otterbein, Zoltan Arany
BACKGROUND: Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children worldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high side-effect profile. New therapeutic approaches are urgently needed. METHODS: Here, we leverage PGC-1α, a powerful transcriptional coactivator known to protect against dystrophy in the mdx murine model of DMD, to search for novel mechanisms of protection against dystrophy...
November 28, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27897348/enzymatic-activity-and-thermodynamic-stability-of-biliverdin-ix%C3%AE-reductase-are-maintained-by-an-active-site-serine
#3
Wen-Ting Chu, Natasha M Nesbitt, Dmitri V Gnatenko, Zongdong Li, Beibei Zhang, Markus A Seeliger, Seamus Browne, Timothy J Mantle, Wadie F Bahou, Jin Wang
Biliverdin reductase IXβ (BLVRB) is a crucial enzyme in heme metabolism. Recent studies in humans have identified a loss-of-function mutation (Ser111Leu) that unmasks a fundamentally important role in hematopoiesis. We have applied experimental and thermodynamic modeling studies to provide further insight into role of the cofactor in substrate accessibility and protein folding properties regulating BLVRB catalytic mechanisms. Site-directed mutagenesis with molecular dynamic (MD) simulations establish the critical role of NAD(P)H-dependent conformational changes on substrate accessibility by forming the "hydrophobic pocket", along with identification of a single key residue (Arg35) modulating NAD(P)H/NADH selectivity...
November 29, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27857208/bright-blue-shifted-fluorescent-proteins-with-cys-in-the-gaf-domain-engineered-from-bacterial-phytochromes-fluorescence-mechanisms-and-excited-state-dynamics
#4
Yusaku Hontani, Daria M Shcherbakova, Mikhail Baloban, Jingyi Zhu, Vladislav V Verkhusha, John T M Kennis
Near-infrared fluorescent proteins (NIR FPs) engineered from bacterial phytochromes (BphPs) are of great interest for in vivo imaging. They utilize biliverdin (BV) as a chromophore, which is a heme degradation product, and therefore they are straightforward to use in mammalian tissues. Here, we report on fluorescence properties of NIR FPs with key alterations in their BV binding sites. BphP1-FP, iRFP670 and iRFP682 have Cys residues in both PAS and GAF domains, rather than in the PAS domain alone as in wild-type BphPs...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27851937/bacteriophytochrome-photoisomerization-proceeds-homogeneously-despite-heterogeneity-in-ground-state
#5
Cheng Wang, Moira L Flanagan, Ryan D McGillicuddy, Haibin Zheng, Alan Ruvim Ginzburg, Xiaojing Yang, Keith Moffat, Gregory S Engel
Phytochromes are red/far-red photoreceptors that are widely distributed in plants and prokaryotes. Ultrafast photoisomerization of a double bond in a biliverdin cofactor or other linear tetrapyrrole drives their photoactivity, but their photodynamics are only partially understood. Multiexponential dynamics were observed in previous ultrafast spectroscopic studies and were attributed to heterogeneous populations of the pigment-protein complex. In this work, two-dimensional photon echo spectroscopy was applied to study dynamics of the bacteriophytochromes RpBphP2 and PaBphP...
November 15, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27817989/heme-oxygenase-1-affects-granulopoiesis-in-mice-through-control-of-myelocyte-proliferation
#6
Karolina Bukowska-Strakova, Maciej Ciesla, Krzysztof Szade, Witold Norbert Nowak, Robert Straka, Agata Szade, Malgorzata Tyszka-Czochara, Karolina Najder, Anna Konturek, Maciej Siedlar, Jozef Dulak, Alicja Jozkowicz
Heme oxygenase-1 (HO-1) is stress-inducible, cytoprotective enzyme degrading heme to carbon monoxide (CO), biliverdin and Fe(2+). We showed that HO-1 knock-out mice (HO-1(-/-)) have a twofold higher level of granulocytes than wild type (WT) mice, despite decreased concentration of granulocyte colony-stimulating factor (G-CSF) in the blood and reduced surface expression of G-CSF receptor on the hematopoietic precursors. This suggests the effect of HO-1 on granulopoiesis. Here we aimed to determine the stage of granulopoiesis regulated by HO-1...
October 21, 2016: Immunobiology
https://www.readbyqxmd.com/read/27778153/phenotypic-characterization-of-a-novel-ho-1-depletion-model-in-the-rat
#7
Vassilios Atsaves, Maria G Detsika, Elpida Poulaki, Hara Gakiopoulou, Elias A Lianos
Although the protective role of HO-1 induction in various forms of kidney disease is well established, mechanisms other than heme catabolism to biliverdin, bilirubin and carbon monoxide have recently been identified. Unraveling these mechanisms requires the generation of appropriate animal models. The present study describes the generation of a HO-1 deficient Hmox1 (-/-) rat model and characterizes its renal and extrarenal phenotype. Hmox1 (-/-) rats had growth retardation and splenomegaly compared to their Hmox1 (+/+) littermates...
October 24, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27766333/carbonyl-bridged-energetic-materials-biomimetic-synthesis-organic-catalytic-synthesis-and-energetic-performances
#8
Yong-An Feng, Hao Qiu, Sa-Sha Yang, Jiang Du, Tong-Lai Zhang
In order to obtain high-performance energetic materials, in this work, carbonyl groups (C[double bond, length as m-dash]O) have been newly introduced as sole bridging groups in the field of energetic materials. To this end, two tailored green methods for the synthesis of carbonyl-bridged energetic compounds have been developed for the first time. One is a biomimetic synthesis, in which the conversion route of heme to biliverdin has been used to obtain metal-containing energetic compounds. The other one is an organocatalysis, in which guanidinium serves as an energetic catalyst to afford other energetic compounds...
October 21, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27760386/spatiotemporal-expression-and-transcriptional-regulation-of-heme-oxygenase-and-biliverdin-reductase-genes-in-zebrafish-danio-rerio-suggest-novel-roles-during-early-developmental-periods-of-heightened-oxidative-stress
#9
Andrew Holowiecki, Britton O'Shields, Matthew J Jenny
Heme oxygenase 1 (HMOX1) degrades heme into biliverdin, which is subsequently converted to bilirubin by biliverdin reductase (BVRa or BVRb) in a manner analogous to the classic anti-oxidant glutathione-recycling pathway. To gain a better understanding of the potential antioxidant roles the BVR enzymes may play during development, the spatiotemporal expression and transcriptional regulation of zebrafish hmox1a, bvra and bvrb were characterized under basal conditions and in response to pro-oxidant exposure. All three genes displayed spatiotemporal expression patterns consistent with classic hematopoietic progenitors during development...
October 17, 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/27740521/predictive-role-blvra-mrna-expression-in-hepatocellular-cancer
#10
Kristy Na Kubícková, Iva Subhanová, Renáta Konícková, Linda Matousová, Petr Urbánek, Hana Parobková, Martin Kupec, Jirí Pudil, Libor Vítek
:  Introduction and aim. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, the aim of our study was to assess expression of the genes involved in the homeostasis of oxidative stress in patients with HCC. MATERIAL AND METHODS: The study was performed on 32 patients with primary HCC (verified by liver histology in 29 patients) and 27 control subjects (in 11 subjects, liver histology was available either with no or minimal changes in the liver tissue)...
November 2016: Annals of Hepatology
https://www.readbyqxmd.com/read/27738106/biliverdin-reductase-a-attenuates-hepatic-steatosis-by-inhibition-of-glycogen-synthase-kinase-gsk-3%C3%AE-phosphorylation-of-serine-73-of-peroxisome-proliferator-activated-receptor-ppar-%C3%AE
#11
Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Abdulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease is the most rapidly growing form of liver disease and if left untreated can result in non-alcoholic steatohepatitis, ultimately resulting in liver cirrhosis and failure. Biliverdin reductase A (BVRA) is a multifunctioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA functions as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase 3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27704083/fiber-enhanced-raman-spectroscopic-analysis-as-a-novel-method-for-diagnosis-and-monitoring-of-diseases-related-to-hyperbilirubinemia-and-hyperbiliverdinemia
#12
Di Yan, Christian Domes, Robert Domes, Timea Frosch, Jürgen Popp, Mathias W Pletz, Torsten Frosch
Fiber enhanced resonance Raman spectroscopy (FERS) is introduced for chemically selective and ultrasensitive analysis of the biomolecules hematin, hemoglobin, biliverdin, and bilirubin. The abilities for analyzing whole intact, oxygenated erythrocytes are proven, demonstrating the potential for the diagnosis of red blood cell related diseases, such as different types of anemia and hemolytic disorders. The optical fiber enables an efficient light-guiding within a miniaturized sample volume of only a few micro-liters and provides a tremendously improved analytical sensitivity (LODs of 0...
October 17, 2016: Analyst
https://www.readbyqxmd.com/read/27699111/multiphoton-excited-hemoglobin-fluorescence-and-third-harmonic-generation-for-non-invasive-microscopy-of-stored-blood
#13
Ilyas Saytashev, Rachel Glenn, Gabrielle A Murashova, Sam Osseiran, Dana Spence, Conor L Evans, Marcos Dantus
Red blood cells (RBC) in two-photon excited fluorescence (TPEF) microscopy usually appear as dark disks because of their low fluorescent signal. Here we use 15fs 800nm pulses for TPEF, 45fs 1060nm pulses for three-photon excited fluorescence, and third harmonic generation (THG) imaging. We find sufficient fluorescent signal that we attribute to hemoglobin fluorescence after comparing time and wavelength resolved spectra of other expected RBC endogenous fluorophores: NADH, FAD, biliverdin, and bilirubin. We find that both TPEF and THG microscopy can be used to examine erythrocyte morphology non-invasively without breaching a blood storage bag...
September 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27688756/blue-protein-with-red-fluorescence
#14
Swagatha Ghosh, Chi-Li Yu, Daniel J Ferraro, Sai Sudha, Samir Kumar Pal, Wayne F Schaefer, David T Gibson, S Ramaswamy
The walleye (Sander vitreus) is a golden yellow fish that inhabits the Northern American lakes. The recent sightings of the blue walleye and the correlation of its sighting to possible increased UV radiation have been proposed earlier. The underlying molecular basis of its adaptation to increased UV radiation is the presence of a protein (Sandercyanin)-ligand complex in the mucus of walleyes. Degradation of heme by UV radiation results in the formation of Biliverdin IXα (BLA), the chromophore bound to Sandercyanin...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27671773/characterization-of-heme-oxygenase-and-biliverdin-reductase-gene-expression-in-zebrafish-danio-rerio-basal-expression-and-response-to-pro-oxidant-exposures
#15
Andrew Holowiecki, Britton O'Shields, Matthew J Jenny
While heme is an important cofactor for numerous proteins, it is highly toxic in its unbound form and can perpetuate the formation of reactive oxygen species. Heme oxygenase enzymes (HMOX1 and HMOX2) degrade heme into biliverdin and carbon monoxide, with biliverdin subsequently being converted to bilirubin by biliverdin reductase (BVRa or BVRb). As a result of the teleost-specific genome duplication event, zebrafish have paralogs of hmox1 (hmox1a and hmox1b) and hmox2 (hmox2a and hmox2b). Expression of all four hmox paralogs and two bvr isoforms were measured in adult tissues (gill, brain and liver) and sexually dimorphic differences were observed, most notably in the basal expression of hmox1a, hmox2a, hmox2b and bvrb in liver samples...
November 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27634590/proteomic-analysis-of-acetaminophen-induced-hepatotoxicity-and-identification-of-heme-oxygenase-1-as-a-potential-plasma-biomarker-of-liver-injury
#16
Yuan Gao, Zhijun Cao, Xi Yang, Mohamed A Abdelmegeed, Jinchun Sun, Si Chen, Richard D Beger, Kelly Davis, William F Salminen, Byoung-Joon Song, Donna L Mendrick, Li-Rong Yu
Overdose of acetaminophen (APAP) is a major cause of acute liver failure. To identify pathways related to hepatotoxicity and potential biomarkers of liver injury, a proteomic approach of (16) O/(18) O labeling and 2D-LC-MS/MS was used to analyze liver tissues from rats at 6 and 24 h post-treatment with low (100 mg/kg) and high (1250 mg/kg) doses of APAP. The analysis revealed that molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner...
September 16, 2016: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/27626166/the-non-canonical-functions-of-the-heme-oxygenases
#17
Luca Vanella, Ignazio Barbagallo, Daniele Tibullo, Stefano Forte, Agata Zappalà, Giovanni Li Volti
Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin with a concurrent release of iron, which can drive the synthesis of ferritin for iron sequestration. Most of the studies so far were directed at evaluating the protective effect of these enzymes because of their ability to generate antioxidant and antiapoptotic molecules such as CO and bilirubin. Recent evidences are suggesting that HO may possess other important physiological functions, which are not related to its enzymatic activity and for which we would like to introduce for the first time the term "non canonical functions"...
September 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27604527/heme-oxygenases-in-cardiovascular-health-and-disease
#18
REVIEW
Anita Ayer, Abolfazl Zarjou, Anupam Agarwal, Roland Stocker
Heme oxygenases are composed of two isozymes, Hmox1 and Hmox2, that catalyze the degradation of heme to carbon monoxide (CO), ferrous iron, and biliverdin, the latter of which is subsequently converted to bilirubin. While initially considered to be waste products, CO and biliverdin/bilirubin have been shown over the last 20 years to modulate key cellular processes, such as inflammation, cell proliferation, and apoptosis, as well as antioxidant defense. This shift in paradigm has led to the importance of heme oxygenases and their products in cell physiology now being well accepted...
October 2016: Physiological Reviews
https://www.readbyqxmd.com/read/27581999/farnesyl-biliverdins-ix%C3%AE-are-novel-ligands-of-biliproteins-from-moths-of-the-noctuoidea-superfamily-a-chemosystematic-view-of-the-lepidoptera
#19
Hartmut Kayser, Manfred Nimtz
Bilins, derived from biliverdin IXα, are known from animals, plants and microorganisms, where they play vital roles as light-absorbing pigments. Bilins occur also in many insects. Recently, we discovered in insects a novel structural type of bilins with a farnesyl substituent at pyrrole ring A of biliverdin IXα. The first of these unusual bilins with a molecular mass of 852 (C48H60O10N4) was identified in Cerura vinula, subsequently in Spodoptera littoralis; both species are members of the Noctuoidea superfamily of moths...
August 28, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27565814/cystathionine-%C3%AE-synthase-and-pgrmc1-as-co-sensors
#20
Yasuaki Kabe, Takehiro Yamamoto, Mayumi Kajimura, Yuki Sugiura, Ikko Koike, Mitsuyo Ohmura, Takashi Nakamura, Yasuhito Tokumoto, Hitoshi Tsugawa, Hiroshi Handa, Takuya Kobayashi, Makoto Suematsu
Heme oxygenase (HO) is a mono-oxygenase utilizing heme and molecular oxygen (O2) as substrates to generate biliverdin-IXα and carbon monoxide (CO). HO-1 is inducible under stress conditions, while HO-2 is constitutive. A balance between heme and CO was shown to regulate cell death and survival in many experimental models. However, direct molecular targets to which CO binds to regulate cellular functions remained to be fully examined. We have revealed novel roles of CO-responsive proteins, cystathionine β-synthase (CBS) and progesterone receptor membrane component 1 (PGRMC1), in regulating cellular functions...
August 24, 2016: Free Radical Biology & Medicine
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