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https://www.readbyqxmd.com/read/28206992/heme-oxygenase-1-promoter-polymorphisms-do-they-modulate-neonatal-hyperbilirubinemia
#1
M Kaplan, R J Wong, D K Stevenson
The role of genetic factors in the modulation of serum bilirubin levels and the pathophysiology of neonatal hyperbilirubinemia is being increasingly recognized. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme by which heme is catabolized to biliverdin and thence to bilirubin, with the simultaneous release of equimolar quantities of ferrous iron (Fe(3+)) and carbon monoxide. Polymorphisms of the HO-1 gene promoter may modulate transcriptional activity, thereby augmenting or attenuating HO-1 expression with resultant modulation of the production of bilirubin...
February 16, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28198575/tat-biliverdin-reductase-a-protects-ins-1-cells-from-human-islet-amyloid-polypeptide-induced-cytotoxicity-by-alleviating-oxidative-stress-and-er-stress
#2
Su Jin Lee, Hyung Kyung Kang, Won Sik Eum, Jinseu Park, Soo Young Choi, Hyeok Yil Kwon
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28186648/the-recipient-s-heme-oxygenase-1-promoter-region-polymorphism-is-associated-with-cardiac-allograft-vasculopathy
#3
Kathrin Freystaetter, Martin Andreas, Martin Bilban, Thomas Perkmann, Alexandra Kaider, Marco Masetti, Alfred Kocher, Michael Wolzt, Andreas Zuckermann
BACKGROUND: Heme oxygenase-1 (HO-1) catalyses the degradation of heme to biliverdin, free iron and carbon monoxide. The promoter region contains a highly polymorphic (GT)n repeat, where shorter (GT)n repeat sequences are linked to higher transcriptional activity, which was shown to correlate with a cytoprotective effect. Higher HO-1 levels may protect from cardiac allograft vasculopathy. METHODS: Cardiac allograft recipients transplanted between 1988 and 2012 were analysed for the HO-1 (GT)n repeat polymorphism using PCR and DNA fragment analysis with capillary electrophoresis...
February 10, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28175984/three-bilindione-isomers-synthesis-characterization-and-reactivity-of-biliverdin-analogs
#4
Jun-Fei Wang, Fang Ma, Hao-Ling Sun, Jing Zhang, Jun-Long Zhang
Linear tetrapyrrole is the core structure of light-sensitive native cofactors such as phycocyanobilin, phytochromobilin and bile pigments, which attracts increasing attention in biomimetic chemistry, photochemistry and coordination chemistry. To decipher the relationship between structures and functions, in this work, we firstly reported the synthesis, isolation and characterization of three bilindione isomers (ZZZ, syn, syn, syn 1, EZE, syn, syn, anti 2 and EZE, anti, syn, anti 3) bearing meso-pentafluorophenyl groups...
February 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28169272/a-substrate-bound-structure-of-cyanobacterial-biliverdin-reductase-identifies-stacked-substrates-as-critical-for-activity
#5
Haruna Takao, Kei Hirabayashi, Yuki Nishigaya, Haruna Kouriki, Tetsuko Nakaniwa, Yoshinori Hagiwara, Jiro Harada, Hideaki Sato, Toshimasa Yamazaki, Yoichi Sakakibara, Masahito Suiko, Yujiro Asada, Yasuhiro Takahashi, Ken Yamamoto, Keiichi Fukuyama, Masakazu Sugishima, Kei Wada
Biliverdin reductase catalyses the last step in haem degradation and produces the major lipophilic antioxidant bilirubin via reduction of biliverdin, using NAD(P)H as a cofactor. Despite the importance of biliverdin reductase in maintaining the redox balance, the molecular details of the reaction it catalyses remain unknown. Here we present the crystal structure of biliverdin reductase in complex with biliverdin and NADP(+). Unexpectedly, two biliverdin molecules, which we designated the proximal and distal biliverdins, bind with stacked geometry in the active site...
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28168030/eggshell-coloration-and-its-importance-in-postmating-sexual-selection
#6
Miroslav Poláček, Matteo Griggio, Ivan Mikšík, Michaela Bartíková, Manfred Eckenfellner, Herbert Hoi
Avian eggshell color seems to fulfill multiple functions, some of them being structural and others signaling. In this study, we tested whether or not eggshell coloration may play a role in sexual selection of Tree Sparrows (Passer montanus). According to the "Sexually selected eggshell coloration" hypothesis, eggshell coloration signals female, egg or chick quality and males adjust parental investment according to this signal. Eggs of this species are covered with brown spots and patches, and variation between clutches is high...
February 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28161963/effects-of-heme-degradation-products-on-reactivation-of-latent-hiv-1
#7
P Shankaran, M Madlenakova, V Hajkova, D Jilich, I Svobodova, A Horinek, Y Fujikura, Z Melkova
Human immunodeficiency virus (HIV-1) infection can be currently controlled by combined antiretroviral therapy, but a sterilizing cure is not achievable as this therapy does not target persistent HIV-1 in latent reservoirs. Therefore, different latency reversal agents are intensively explored in various models. We have previously observed that heme arginate, a drug approved for human use, reveals a strong synergism with PKC inducers in reactivation of the latent provirus. Heme is physiologically decomposed by heme oxygenases into 3 degradation products: iron (Fe2+), carbon monoxide (CO) and biliverdin which is further converted to bilirubin by biliverdin reductase...
February 6, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28144740/hibernation-reduces-cellular-damage-caused-by-warm-hepatic-ischemia-reperfusion-in-ground-squirrels
#8
Jessica P Otis, Amanda C Pike, Jose R Torrealba, Hannah V Carey
During the hibernation season, livers from 13-lined ground squirrels (Ictidomys tridecemlineatus) are resistant to damage induced by ex vivo, cold ischemia-warm reperfusion (IR) compared with livers from summer squirrels or rats. Here, we tested the hypothesis that hibernation also reduces damage to ground squirrel livers in an in vivo, warm IR model, which more closely resembles complications associated with traumatic injury or surgical interventions. We also examined whether protection is mediated by two metabolites, inosine and biliverdin, that are elevated in ground squirrel liver during interbout arousals...
January 31, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28142266/inflammatory-microenvironment-persists-after-bone-healing-in-intra-articular-ankle-fractures
#9
Samuel B Adams, Elizabeth M Leimer, Lori A Setton, Richard D Bell, Mark E Easley, Janet L Huebner, Thomas V Stabler, Virginia B Kraus, Steven A Olson, Dana L Nettles
BACKGROUND: Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA. METHODS: Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection...
January 1, 2017: Foot & Ankle International
https://www.readbyqxmd.com/read/28120965/density-functional-theory-studies-on-the-conversion-of-hydroxyheme-to-iron-verdoheme-in-the-presence-of-dioxygen
#10
Mahin Gheidi, Nasser Safari, Mansour Zahedi
Detailed insight into the second step of heme degradation by heme oxygenase, oxophlorin to verdoheme and biliverdin, is presented. Density functional theory methods are reported for the conversion of oxophlorin to verdoheme. Since it is currently unclear whether dioxygen binding to iron oxophlorin is followed by a reduction or not, in this work we have focused on the difference in reactivity between [(Im)(O2˙)Fe(III)(PO˙)] (PO˙ is the oxophlorin dianion radical) and [(Im)(O2˙)Fe(III)(PO)](-) (PO is the oxophlorin trianion)...
January 25, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28108964/heme-oxygenase-1-defects-lead-to-reduced-chlorophyll-in-brassica-napus
#11
Lixia Zhu, Zonghui Yang, Xinhua Zeng, Jie Gao, Jie Liu, Bin Yi, Chaozhi Ma, Jinxiong Shen, Jinxing Tu, Tingdong Fu, Jing Wen
We previously described a Brassica napus chlorophyll-deficient mutant (ygl) with yellow-green seedling leaves and mapped the related gene, BnaC.YGL, to a 0.35 cM region. However, the molecular mechanisms involved in this chlorophyll defect are still unknown. In this study, the BnaC07.HO1 gene (equivalent to BnaC.YGL) was isolated by the candidate gene approach, and its function was confirmed by genetic complementation. Comparative sequencing analysis suggested that BnaC07.HO1 was lost in the mutant, while a long noncoding-RNA was inserted into the promoter of the homologous gene BnaA07...
January 20, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#12
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28045510/anaerobic-heme-degradation-chuy-is-an-anaerobilin-reductase-that-exhibits-kinetic-cooperativity
#13
Joseph W LaMattina, Michael Delrossi, Katherine G Uy, Nicholas D Keul, David B Nix, Anudeep R Neelam, William N Lanzilotta
Heme catabolism is an important biochemical process that many bacterial pathogens utilize to acquire iron. However, tetrapyrrole catabolites can be reactive and often require further processing for transport out of the cell or conversion to another useful cofactor. In previous work, we presented in vitro evidence of an anaerobic heme degradation pathway in Escherichia coli O157:H7. Consistent with reactions that have been reported for other radical S-adenosyl-l-methionine methyltransferases, ChuW transfers a methyl group to heme by a radical-mediated mechanism and catalyzes the β-scission of the porphyrin macrocycle...
January 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/27992676/haem-oxygenase-1-polymorphisms-can-affect-hcv-replication-and-treatment-responses-with-different-efficacy-in-humanized-mice
#14
Janine Kah, Tassilo Volz, Marc Lütgehetmann, Anne Groth, Ansgar W Lohse, Gisa Tiegs, Gabriele Sass, Maura Dandri
BACKGROUND & AIMS: Enhancement of host anti-oxidant enzymes, such as haemoxygenase-1, may attenuate virus-mediated hepatocyte injury, while the induction of HO-1 by cobalt-protoporphyrin-IX (CoPP) administration, as the application of its haem degradation product biliverdin (BV), was shown to hinder HCV replication in vitro. In addition, (GT)n -repeats length in the polymorphic region of the HO-1 promoter may affect HO-1 expression and responsiveness to infection and disease severity...
December 19, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27990801/tryptophan-rich-sensory-protein-translocator-protein-tspo-from-cyanobacterium-fremyella-diplosiphon-binds-a-broad-range-of-functionally-relevant-tetrapyrroles
#15
Andrea W U Busch, Zachary WareJoncas, Beronda L Montgomery
Tryptophan-rich sensory protein/translocator protein (TSPO) is a membrane protein involved in stress adaptation in the cyanobacterium Fremyella diplosiphon. Characterized mammalian and proteobacterial TSPO homologues bind tetrapyrroles and cholesterol ligands. We investigated the ligand binding properties of TSPO from F. diplosiphon (FdTSPO1), which was functionally characterized in prior genetic studies. Two additional TSPO proteins (FdTSPO2 and FdTSPO3) are present in F. diplosiphon; they are similar in size to reported bacterial TSPOs and smaller than FdTSPO1...
December 19, 2016: Biochemistry
https://www.readbyqxmd.com/read/27919686/structural-and-functional-study-of-chuy-from-escherichia-coli-strain-cft073
#16
Hun Kim, Akhilesh Kumar Chaurasia, Truc Kim, Jongkeun Choi, Sung Chul Ha, Doyoun Kim, Kyeong Kyu Kim
The uropathogenic Escherichia coli strain CFT073 contains multiple iron and heme transport systems, which facilitate infection of the host urinary tract. To elucidate the molecular and cellular function of ChuY, a hypothetical gene in the heme degradation/utilization pathway, we solved the crystal structure of ChuY at 2.4 Å resolution. ChuY has high structural homology with human biliverdin and flavin reductase. We confirmed that ChuY has flavin mononucleotide (FMN) reductase activity, using NAD(P)H as a cofactor, and shows porphyrin ring binding affinity...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908781/heme-oxygenase-1-metabolite-biliverdin-not-iron-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication
#17
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...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27906108/heme-oxygenase-and-carbon-monoxide-protect-from-muscle-dystrophy
#18
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
#19
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 undertaken experimental and thermodynamic modeling studies to provide further insight into the 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 NADPH/NADH selectivity...
February 3, 2017: 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
#20
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
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