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Hemopexin

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https://www.readbyqxmd.com/read/28420988/heme-as-a-target-for-therapeutic-interventions
#1
REVIEW
Stephan Immenschuh, Vijith Vijayan, Sabina Janciauskiene, Faikah Gueler
Heme is a complex of iron and the tetrapyrrole protoporphyrin IX with essential functions in aerobic organisms. Heme is the prosthetic group of hemoproteins such as hemoglobin and myoglobin, which are crucial for reversible oxygen binding and transport. By contrast, high levels of free heme, which may occur in various pathophysiological conditions, are toxic via pro-oxidant, pro-inflammatory and cytotoxic effects. The toxicity of heme plays a major role for the pathogenesis of prototypical hemolytic disorders including sickle cell disease and malaria...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28413025/biochemical-and-biological-attributes-of-matrix-metalloproteinases
#2
Ning Cui, Min Hu, Raouf A Khalil
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in the degradation of various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28400318/hemopexin-counteracts-systolic-dysfunction-induced-by-heme-driven-oxidative-stress
#3
Giada Ingoglia, Can Martin Sag, Nikolai Rex, Lucia De Franceschi, Francesca Vinchi, James Cimino, Sara Petrillo, Stefan Wagner, Klaus Kreitmeier, Lorenzo Silengo, Fiorella Altruda, Lars S Maier, Emilio Hirsch, Alessandra Ghigo, Emanuela Tolosano
Heart failure is a leading cause of morbidity and mortality in patients affected by different disorders associated to intravascular hemolysis. The leading factor is the presence of pathologic amount of pro-oxidant free heme in the bloodstream, due to the exhaustion of the natural heme scavenger Hemopexin (Hx). Here, we evaluated whether free heme directly affects cardiac function, and tested the therapeutic potential of replenishing serum Hx for increasing serum heme buffering capacity. The effect of heme on cardiac function was assessed in vitro, on primary cardiomyocytes and H9c2 myoblast cell line, and in vivo, in Hx(-/-) mice and in genetic and acquired mouse models of intravascular hemolysis...
April 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28389660/characteristics-of-the-heme-catabolic-pathway-in-mild-unconjugated-hyperbilirubinemia-and-their-associations-with-inflammation-and-disease-prevention
#4
Christine Mölzer, Marlies Wallner, Carina Kern, Anela Tosevska, René Zadnikar, Daniel Doberer, Rodrig Marculescu, Karl-Heinz Wagner
Heme catabolism exerts physiological functions that impact health through depressing inflammation. Upon reactive pathway progression, as in Gilbert's Syndrome (GS; UGT1A1*28 polymorphism), aggravated health effects have been determined. Based on lower inflammation and improved metabolic health reported for GS, inter-group differences in heme catabolism were explored. Therefore, a case-control study including 120 fasted, healthy, age- and gender matched subjects with/without GS, was conducted. Genetic expressions of HMOX-1 and BLVRA were measured...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28314763/endothelial-dysfunction-inhibits-the-ability-of-haptoglobin-to-prevent-hemoglobin-induced-hypertension
#5
Jan A Graw, Binglan Yu, Emanuele Rezoagli, H Shaw Warren, Emmanuel S Buys, Donald B Bloch, Warren M Zapol
BACKGROUND: Intravascular hemolysis produces injury in a variety of human diseases including hemoglobinopathies, malaria, and sepsis. The adverse effects of increased plasma hemoglobin are partly mediated by depletion of nitric oxide (NO) and result in vasoconstriction. Circulating plasma proteins haptoglobin and hemopexin scavenge extracellular hemoglobin and cell-free heme, respectively. METHODS: The ability of human haptoglobin or hemopexin to inhibit the adverse effects of NO-scavenging by circulating murine hemoglobin was tested in C57Bl/6 mice...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28299732/structural-studies-of-matrix-metalloproteinase-by-x-ray-diffraction
#6
Elena Decaneto, Wolfgang Lubitz, Hideaki Ogata
Matrix Metalloproteinases (MMPs) are a family of proteolytic enzymes whose endopeptidase activity is dependent on the presence of specific metal ions. MT1-MMP (or MMP-14), which has been implicated in tumor progression and cellular invasion, contains a membrane-spanning region located C-terminal to a hemopexin-like domain and an N-terminal catalytic domain. We recombinantly expressed the catalytic domain of human MT1-MMP in E. coli and purified it from inclusion bodies using a refolding protocol that yielded significant quantities of active protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28286877/il-22-controls-iron-dependent-nutritional-immunity-against-systemic-bacterial-infections
#7
Kei Sakamoto, Yun-Gi Kim, Hideki Hara, Nobuhiko Kamada, Gustavo Caballero-Flores, Emanuela Tolosano, Miguel P Soares, José L Puente, Naohiro Inohara, Gabriel Núñez
Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28242648/identification-of-novel-chondroprotective-mediators-in-resolving-inflammatory-exudates
#8
Magdalena K Kaneva, Karin V Greco, Sarah E Headland, Trinidad Montero-Melendez, Prashant Mori, Kevin Greenslade, Costantino Pitzalis, Adrian Moore, Mauro Perretti
We hypothesized that exudates collected at the beginning of the resolution phase of inflammation might be enriched for tissue protective molecules; thus an integrated cellular and molecular approach was applied to identify novel chondroprotective bioactions. Exudates were collected 6 h (inflammatory) and 24 h (resolving) following carrageenan-induced pleurisy in rats. The resolving exudate was subjected to gel filtration chromatography followed by proteomics, identifying 61 proteins. Fractions were added to C28/I2 chondrocytes, grown in micromasses, ions with or without IL-1β or osteoarthritic synovial fluids for 48 h...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28238792/an-all-recombinant-protein-based-culture-system-specifically-identifies-hematopoietic-stem-cell-maintenance-factors
#9
Aki Ieyasu, Reiko Ishida, Takaharu Kimura, Maiko Morita, Adam C Wilkinson, Kazuhiro Sudo, Toshinobu Nishimura, Jun Ohehara, Yoko Tajima, Chen-Yi Lai, Makoto Otsu, Yukio Nakamura, Hideo Ema, Hiromitsu Nakauchi, Satoshi Yamazaki
Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28173805/serum-proteomic-profiles-in-ckcs-with-mitral-valve-disease
#10
Chiara Locatelli, Cristian Piras, Giulia Riscazzi, Isabella Alloggio, Ilaria Spalla, Alessio Soggiu, Viviana Greco, Luigi Bonizzi, Paola Roncada, Paola G Brambilla
BACKGROUND: Myxomatous mitral valve disease (MVD) is the most common acquired heart disease in dogs, and the Cavalier King Charles Spaniel (CKCS) is the most studied breed because of the high prevalence, early onset and hereditary component evidenced in the breed. MVD has different severity levels, and there are many practical limitations in identifying its asymptomatic stages. Proteomic techniques are valuable for studying the proteins and peptides involved in cardiovascular diseases, including the period prior to the clinical onset of the disease...
February 7, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28152051/hemoglobin-induced-cell-trauma-indirectly-influences-endothelial-tlr9-activity-resulting-in-pulmonary-vascular-smooth-muscle-cell-activation
#11
Zoe Loomis, Paul Eigenberger, Katherine Redinius, Christina Lisk, Vijaya Karoor, Eva Nozik-Grayck, Scott K Ferguson, Kathryn Hassell, Rachelle Nuss, Kurt Stenmark, Paul Buehler, David C Irwin
It is now well established that both inherited and acquired forms of hemolytic disease can promote pulmonary vascular disease consequent of free hemoglobin (Hb) induced NO scavenging, elevations in reactive oxygen species and lipid peroxidation. It has recently been reported that oxidative stress can activate NFkB through a toll-like receptor 9 (TLR9) mediated pathway; further, TLR9 can be activated by either nuclear or mitochondrial DNA liberated by stress induced cellular trauma. We hypothesis that Hb induced lipid peroxidation and subsequent endothelial cell trauma is linked to TLR9 activation, resulting in IL-6 mediated pulmonary smooth muscle cell proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28143953/hemolytic-anemia-repressed-hepcidin-level-without-hepatocyte-iron-overload-lesson-from-g%C3%A3-nther-disease-model
#12
Sarah Millot, Constance Delaby, Boualem Moulouel, Thibaud Lefebvre, Nathalie Pilard, Nicolas Ducrot, Cécile Ged, Philippe Lettéron, Lucia de Franceschi, Jean Charles Deybach, Carole Beaumont, Laurent Gouya, Hubert De Verneuil, Saïd Lyoumi, Hervé Puy, Zoubida Karim
Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1...
February 2017: Haematologica
https://www.readbyqxmd.com/read/28142234/plasma-protein-binding-structure-activity-relationships-related-to-the-n-terminus-of-daptomycin
#13
Elena K Schneider, Johnny X Huang, Vincenzo Carbone, Meiling Han, Yan Zhu, Sue Nang, Keith K Khoo, Johnson Mak, Matthew A Cooper, Jian Li, Tony Velkov
Daptomycin is a lipopeptide antibiotic that is highly bound to plasma proteins. To date, the plasma components and structure-activity relationships responsible for the plasma protein binding profile of daptomycin remain uncharacterized. In the present study we have employed a surface plasmon resonance assay together with molecular docking techniques to investigate the plasma protein binding structure-activity relationships related to the N-terminal fatty acyl of daptomycin. Three compounds were investigated: (1) native daptomycin, which displays an N-terminal n-decanoyl fatty acid side chain, and two analogues with modifications to the N-terminal fatty acyl chain; (2) des-acyl daptomycin; and (3) acetyl-daptomycin...
February 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28119529/physiologic-and-genetic-evidence-links-hemopexin-to-triglycerides-in-mice-and-humans
#14
H A Lawson, M Zayed, J P Wayhart, E Fabbrini, L Love-Gregory, S Klein, C F Semenkovich
BACKGROUND/OBJECTIVES: Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. SUBJECTS/METHODS: Hemopexin (HPX) was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F16 advanced intercross between the LG/J and SM/J strains of mice...
April 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28034890/a-novel-mechanism-regulating-human-platelet-activation-by-mmp-2-mediated-par1-biased-signaling
#15
Manuela Sebastiano, Stefania Momi, Emanuela Falcinelli, Loredana Bury, Marc Hoylaerts, Paolo Gresele
Platelets contain and release several matrix metalloproteinases (MMPs). Among these, active MMP-2 enhances platelet aggregation by favouring the activation of phosphatidyl-inositol-3- kinase (PI3-K) and contributes to arterial thrombosis. The platelet surface target of MMP-2 and the mechanism through which it primes platelets to respond to subsequent stimuli are still unknown. We show that active MMP-2 enhances platelet activation induced by weak stimuli by cleaving PAR1 at a non-canonical extracellular site different from the thrombin-cleavage site, and thus starts biased receptor signaling triggering only some of the signaling pathways normally activated by full PAR1 agonism...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/28030762/placental-proteomics-provides-insights-into-pathophysiology-of-pre-eclampsia-and-predicts-possible-markers-in-plasma
#16
Sheon Mary, Mahesh J Kulkarni, Dipankar Malakar, Sadhana R Joshi, Savita S Mehendale, Ashok P Giri
Pre-eclampsia is a hypertensive disorder characterized by the new onset of hypertension >140/90 mmHg and proteinuria after the 20th week of gestation. The disorder is multifactorial and originates with abnormal placentation. Comparison of the placental proteome of normotensive (n = 25) and pre-eclamptic (n = 25) patients by gel-free proteomic techniques identified a total of 2145 proteins in the placenta of which 180 were differentially expressed (>1.3 fold, p < 0.05). Gene ontology enrichment analysis of biological process suggested that the differentially expressed proteins belonged to various physiological processes such as angiogenesis, apoptosis, oxidative stress, hypoxia, and placental development, which are implicated in the pathophysiology of pre-eclampsia...
January 26, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/27864463/increased-brain-hemopexin-levels-improve-outcomes-after-intracerebral-hemorrhage
#17
Jenna L Leclerc, Juan Santiago-Moreno, Alex Dang, Andrew S Lampert, Pedro E Cruz, Awilda M Rosario, Todd E Golde, Sylvain Doré
Following intracerebral hemorrhage (ICH), extracellular heme precipitates secondary brain injury, which results in irreversible brain damage and enduring neurological deficits. Hemopexin (Hpx) is an endogenous protein responsible for scavenging heme, thereby modulating its intrinsic proxidant/proinflammatory properties. Although Hpx is present in the brain, the endogenous levels are insufficient to combat the massive heme overload following ICH. We hypothesized that increasing brain Hpx levels would improve ICH outcomes...
January 1, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27768920/nano-lc-ms-ms-for-the-identification-of-proteins-trapped-in-sorbent-cartridges-used-for-coupled-plasma-filtration-adsorption-treatments-of-healthy-pigs
#18
Donatella Nardiello, Clelia Prattichizzo, Maria Teresa Rocchetti, Loreto Gesualdo, Diego Centonze
A dedicated proteomic approach based on nano-Liquid Chromatography coupled with tandem mass spectrometry in ion trap is proposed for the analysis of proteins trapped in sorbent resin cartridges used to remove inflammatory mediators from blood by coupled plasma filtration adsorption (CPFA). The final purpose of the proposed proteomic approach was to obtain a reference map of plasma proteins trapped in CPFA sorbents used for the extracorporeal blood purification of healthy pigs, with the potential impact to design new bio-filters able to control the inflammatory imbalance under pathological conditions, such as severe sepsis...
January 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27754420/effects-of-mutations-on-structure-function-relationships-of-matrix-metalloproteinase-1
#19
Warispreet Singh, Gregg B Fields, Christo Z Christov, Tatyana G Karabencheva-Christova
Matrix metalloproteinase-1 (MMP-1) is one of the most widely studied enzymes involved in collagen degradation. Mutations of specific residues in the MMP-1 hemopexin-like (HPX) domain have been shown to modulate activity of the MMP-1 catalytic (CAT) domain. In order to reveal the structural and conformational effects of such mutations, a molecular dynamics (MD) study was performed of in silico mutated residues in the X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP)...
October 14, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27716784/the-mechanism-of-proinflammatory-hdl-generation-in-sickle-cell-disease-is-linked-to-cell-free-hemoglobin-via-haptoglobin
#20
Xiang Ji, Yimin Feng, Hui Tian, Wei Meng, Weiling Wang, Na Liu, Jun Zhang, Lingshu Wang, Jian Wang, Haiqing Gao
In sickle cell disease (SCD), the inflammatory properties of high-density lipoprotein (HDL) can be changed by cell-free hemoglobin (Hb), which is released into the blood during hemolysis. Hb in the plasma of SCD patients or mice can bind with HDL specifically inducing an inflammatory reaction. In our study, we found increased amounts of inflammatory factor proteins in the chronic oxidative state of SCD with higher levels of Hb, haptoglobin (Hp) and hemopexin (Hx) in the apolipoprotein A-I (ApoA-1) particles of HDL and the role of HDL is changed from being anti-inflammatory to proinflammatory...
2016: PloS One
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