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Nicolas S Merle, Anne Grunenwald, Marie-Lucile Figueres, Sophie Chauvet, Marie Daugan, Samantha Knockaert, Tania Robe-Rybkine, Remi Noe, Olivia May, Marie Frimat, Nathan Brinkman, Thomas Gentinetta, Sylvia Miescher, Pascal Houillier, Veronique Legros, Florence Gonnet, Olivier P Blanc-Brude, Marion Rabant, Regis Daniel, Jordan D Dimitrov, Lubka T Roumenina
Intravascular erythrocyte destruction, accompanied by the release of pro-oxidative and pro-inflammatory components hemoglobin and heme, is a common event in the pathogenesis of numerous diseases with heterogeneous etiology and clinical features. A frequent adverse effect related to massive hemolysis is the renal injury and inflammation. Nevertheless, it is still unclear whether heme--a danger-associated molecular pattern--and ligand for TLR4 or upstream hemolysis-derived products are responsible for these effects...
2018: Frontiers in Immunology
Gibeom Kwon, Sungho Ghil
Warm temperature acclimation-associated 65-kDa protein (Wap65) is known to respond to elevated water temperatures and the corresponding gene from several fish species has been cloned. Expression of Wap65 gene is induced by various physiological stresses, such as increase in water temperature, immune response and heavy metal exposure. Two isolated Wap65 genes, Wap65-1 and Wap65-2, display distinct tissue distribution and physiological functions despite high sequence homology. In a previous study, we identified the Wap65-1 gene (kmWap65-1) from Kumgang fat minnow, Rhynchocypris kumgangensis, a small freshwater fish endemic to Korea...
March 15, 2018: Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
Ulrik Dolberg Anderson, Maya Jälmby, Marijke M Faas, Stefan R Hansson
OBJECTIVE: The aim of this study was to investigate how maternal cell-free fetal hemoglobin and heme impact the scavenger enzyme systems Hemopexin and Heme Oxygenase-1 in patients with preeclampsia (PE). The secondary aims were to evaluate these proteins as biomarkers for severity of the clinical manifestation i.e. hypertension, in early- and late onset PE. MATERIAL AND METHODS: Plasma samples taken within the last 24 h before delivery from 135 patients were analyzed, 89 PE and 46 normal pregnancies...
February 15, 2018: Pregnancy Hypertension
Nathella Pavan Kumar, Vaithilingam V Banurekha, Dina Nair, Chandrakumar Dolla, Paul Kumaran, Subash Babu
Tuberculosis (TB) and diabetes mellitus (DM) remain vital disease burdens in developing countries and the dual burden of DM and TB clearly signifies a growing global public health concern. While modulation of iron status biomarkers in TB is well described, very little is known about the association of these markers with TB-DM. To examine the association of circulating iron status biomarkers in TB disease, we examined the systemic levels of ferritin, hepcidin, soluble transferrin receptor (sTfR), transferrin, apotransferrin and hemopexin in pulmonary TB (PTB) individuals with DM (PTB-DM), without DM (PTB) and those with diabetes only (DM)...
January 2018: Tuberculosis
Brant M Wagener, Parker J Hu, Joo-Yeun Oh, Cilina A Evans, Jillian R Richter, Jaideep Honavar, Angela P Brandon, Judy Creighton, Shannon W Stephens, Charity Morgan, Randal O Dull, Marisa B Marques, Jeffrey D Kerby, Jean-Francois Pittet, Rakesh P Patel
BACKGROUND: Trauma is the leading cause of death and disability in patients aged 1-46 y. Severely injured patients experience considerable blood loss and hemorrhagic shock requiring treatment with massive transfusion of red blood cells (RBCs). Preclinical and retrospective human studies in trauma patients have suggested that poorer therapeutic efficacy, increased severity of organ injury, and increased bacterial infection are associated with transfusion of large volumes of stored RBCs, although the mechanisms are not fully understood...
March 2018: PLoS Medicine
Jing Chen-Roetling, Sheng-Kai Ma, Yang Cao, Aishwarya Shah, Raymond F Regan
Hemopexin (Hpx) binds heme with extraordinary affinity, and after haptoglobin may provide a second line of defense against the toxicity of extracellular hemoglobin (Hb). In this series of experiments, the hypothesis that Hpx protects neurons from Hb neurotoxicity was evaluated in murine primary cultures containing neurons and glial cells. Contrary to hypothesis, Hpx increased neuronal loss due to micromolar concentrations of Hb by 4-12-fold, as measured by LDH release assay; conversely, the neurotoxicity of hemin was completely prevented...
March 3, 2018: Journal of Neurochemistry
Jaimie Dufresne, Angelique Florentinus-Mefailoski, Pete Bowden, John G Marshall
The proteins identified from endogenous peptides agreed between serum versus plasma, and tryptic versus non-tryptic peptides, collected by C18 alone and analyzed by liquid chromatography electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS) including amyloids, apolipoproteins, haptoglobin, complements, fibrinogens, hemopexin, antitrypsin and alpha 2 macroglobulin. Precipitation of polypeptides from plasma in 9 vol of 100% organic solvent followed by stepwise extraction of the insoluble pellet with an increasing fraction of water identified thousands of proteins...
February 24, 2018: Analytical Biochemistry
Zhidan Liu, Chunlan Chen, Xiaoyan Li, Chuang Zhao, Zunyuan Li, Wei Liang, Yufang Lin
OBJECTIVE: Cupping therapy has a long history in traditional medicine especially in Asian countries. It was controversial whether cupping induced blisters are beneficial to healing effects, and the formation and content in the blisters remain unexplored. We aimed to identify and compare the molecular components of the blister fluid from the cupping therapy and the scalds to explore the necessary of inducing cupping induced blisters. METHODS: Fluid sample of blisters from fifteen patients receiving cupping therapy (Cupping group) and scald burns (Scald group) were collected in this study...
February 2018: Complementary Therapies in Medicine
Yanling Zhu, Yang Qiu, Mengjia Chen, Yi Zhang, Li Cao, Zhida Su, Yimin Yuan, Aijun Huang, Yinyan Pu, Cheng He
The neural stem cells (NSCs) of the subventricular zone (SVZ) reside within a specialized niche critical for neurogenesis. Hemopexin, a plasma glycoprotein, has been extensively studied as a heme scavenger at the systemic level. However, little is known about its function in the central nervous system, especially in neurogenesis. In the present study, we demonstrate that deletion of hemopexin leads to neurogenic abnormalities in the SVZ/olfactory bulb (OB) pathway. The lateral ventricle is enlarged in hemopexin-deficient mice, and more apoptosis was observed in Dcx+ cells...
February 15, 2018: Cell Death & Disease
Magda Gioia, Giovanni Francesco Fasciglione, Diego Sbardella, Francesca Sciandra, MariaLuisa Casella, Serena Camerini, Marco Crescenzi, Alessandro Gori, Umberto Tarantino, Paola Cozza, Andrea Brancaccio, Massimo Coletta, Manuela Bozzi
Dystroglycan (DG) is a membrane receptor, belonging to the dystrophin-glycoprotein complex (DGC) and formed by two subunits, α-dystroglycan (α-DG) and β-dystroglycan (β -DG). The C-terminal domain of α-DG and the N-terminal extracellular domain of β -DG are connected, providing a link between the extracellular matrix and the cytosol. Under pathological conditions, such as cancer and muscular dystrophies, DG may be the target of metalloproteinases MMP-2 and MMP-9, contributing to disease progression. Previously, we reported that the C-terminal domain α-DG (483-628) domain is particularly susceptible to the catalytic activity of MMP-2; here we show that the α-DG 621-628 region is required to carry out its complete digestion, suggesting that this portion may represent a MMP-2 anchoring site...
2018: PloS One
Junfeng Ma, Miloslav Sanda, Renhuizi Wei, Lihua Zhang, Radoslav Goldman
Aberrant core fucosylation of proteins has been linked to liver diseases. In this study, we carried out multiple reaction monitoring (MRM) quantification of core fucosylated N-glycopeptides of serum proteins partially deglycosylated by a combination of endoglycosidases (endoF1, endoF2, and endoF3). To minimize variability associated with the preparatory steps, the analysis was performed without enrichment of glycopeptides or fractionation of serum besides the nanoRP chromatography. Specifically, we quantified core fucosylation of 22 N-glycopeptides derived from 17 proteins together with protein abundance of these glycoproteins in a cohort of 45 participants (15 disease-free control, 15 fibrosis and 15 cirrhosis patients) using a multiplex nanoUPLC-MS-MRM workflow...
February 7, 2018: Journal of Proteomics
Dunxin Han, Zhongwang Yu, Weili Liu, Dou Yin, Yingyan Pu, Jifeng Feng, Yimin Yuan, Aijun Huang, Li Cao, Cheng He
Spinal cord injury (SCI) is a devastating type of central nervous system (CNS) trauma with limited therapeutic treatments. The polarization of microglia into the M1 or M2 state has been documented to play important roles in the pathogenesis of SCI, although the complete repertoire of underlying factors has not been identified. Interestingly, the time point at which hematomyelia (intramedullary spinal cord hemorrhage) is alleviated coincides with a decrease in the number of M2 microglia. Here the function of Hemopexin (Hpx), a hematogenous glycoprotein, was examined in the crush model of SCI...
February 7, 2018: Cell Death & Disease
Janejira Kittivorapart, Vanja Karamatic Crew, Marieangela C Wilson, Kate J Heesom, Noppadol Siritanaratkul, Ashley M Toye
Hemoglobin E (HbE)/β-thalassemia has a wide spectrum of clinical manifestations that cannot be explained purely by its genetic background. Circulating extracellular vesicles (EVs) are one factor that likely contributes to disease severity. This study has explored the differences in protein composition and quantity between EVs from HbE/β-thalassemic patients and healthy individuals. We used tandem mass tag labeling mass spectrometry to analyze the EV proteins isolated from the plasma of 15 patients compared with the controls...
January 23, 2018: Blood Advances
Xi Wang, Raouf A Khalil
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade 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...
2018: Advances in Pharmacology
Beibei Dong, Zhishen Zhang, Keliang Xie, Yongyan Yang, Yuan Shi, Chenxu Wang, Yonghao Yu
BACKGROUND: Ischemia-reperfusion (I/R) is a critical pathophysiological change of ischemic stroke. Heme-oxygenase-1 (HO-1) is a rate-limiting enzyme of eliminating excessive free heme by combining with hemopexin (HPX), a plasma protein contributing to alleviating infarct size due to ischemia stroke. This study was to investigate whether HPX could improve angiogenesis after cerebral ischemia-reperfusion via up-regulating HO-1. METHODS: Rats were randomly divided into five groups: sham, MCAO, MCAO + Vehicle, MCAO + HPX and MCAO + HPX + protoporphyrin IX (ZnPPIX, an HO-1 inhibitor)...
January 3, 2018: BMC Anesthesiology
Mika Ohta, Aki Sugano, Naoya Hatano, Hirotaka Sato, Hirofumi Shimada, Hitoshi Niwa, Toshiyuki Sakaeda, Hajime Tei, Yoshiyuki Sakaki, Ken-Ichi Yamamura, Yutaka Takaoka
The disease model of familial amyloidotic polyneuropathy-7.2-hMet30 mice-manifests amyloid deposition that consists of a human amyloidogenic mutant transthyretin (TTR) (TTR V30M). Our previous study found amyloid deposits in 14 of 27 7.2-hMet30 mice at 21-24 months of age. In addition, non-fibrillar TTR deposits were found in amyloid-negative 7.2hMet30 mice. These results suggested that TTR amyloidogenesis required not only mutant TTR but also an additional factor (or factors) as an etiologic molecule. To determine the differences in serum proteome in amyloid-positive and amyloid-negative mice in the 7...
December 29, 2017: Transgenic Research
Xi-Ming Yuan, Liam J Ward, Claes Forssell, Nabeel Siraj, Wei Li
BACKGROUND AND PURPOSE: Men differ from women in the manifestation of atherosclerosis and iron metabolism. Intraplaque hemorrhage and hemoglobin (Hb) catabolism by macrophages are associated with atherosclerotic lesion instability. The study aims were to investigate sex differences in (1) lesion severity in relation to blood Hb, (2) iron homeostasis in human carotid plaques, and (3) macrophage polarization within atheroma. METHODS: The carotid artery samples from 39 men and 23 women were immunostained with cell markers for macrophages, smooth muscle cells, ferritin, and TfR1 (transferrin receptor 1), which were further analyzed according to sex in relation to iron, Hb, and lipids in circulation...
December 28, 2017: Stroke; a Journal of Cerebral Circulation
Brenda Mertens, Valérie Orti, Jérôme Vialaret, Philippe Gibert, Aroa Relaño-Ginés, Sylvain Lehmann, Dominique Deville de Périère, Christophe Hirtz
AIM: The present study focused on the research of new biomarkers based on the liquid chromatography-multiple-reaction monitoring (MRM) proteomic profile in whole saliva of patients with periodontitis compared with periodontal healthy patients. METHODS: A 30-min multiplexed liquid chromatography-MRM method was used for absolute quantification of 35 plasma biomarkers in saliva from control patients and patients with periodontitis. RESULTS: Three proteins namely hemopexin, plasminogen and α-fibrinogen were shown to be clearly related to the presence of periodontitis compared with healthy patients...
December 15, 2017: Bioanalysis
James E Louie, Caitlin J Anderson, Katayoun Fayaz M Fomani, Alonye Henry, Trevor Killeen, Narla Mohandas, Karina Yazdanbakhsh, John D Belcher, Gregory M Vercellotti, Patricia A Shi
BACKGROUND: Depletion of haptoglobin (Hp) and hemopexin (Hx) with increase in free hemoglobin and heme are important etiologies of vaso-occlusive complications in sickle cell disease (SCD). This study is the first to show an association between clinical improvement in SCD and repletion of Hp and Hx by therapeutic plasma exchange (TPE) using plasma replacement. STUDY DESIGN AND METHODS: Thirteen fresh-frozen plasma (FFP) units derived from consecutive whole blood donations were thawed at 37°C after 10 months of storage; Hp and Hx concentrations immediately postthaw and after 5 days of refrigerated storage were analyzed by enzyme-linked immunosorbent assay (ELISA)...
February 2018: Transfusion
Tatyana G Karabencheva-Christova, Christo Z Christov, Gregg B Fields
Matrix metalloproteinase-1 (MMP-1) is a zinc-dependent protease that catalyzes hydrolysis of interstitial collagens. A previously reported X-ray crystallographic structure revealed specific interactions between a triple-helical peptide (THP) model of interstitial collagen and the hemopexin-like (HPX) and catalytic (CAT) domains of MMP-1. An NMR-based structure of MMP-1 in a complex with a different THP was also solved, where docking was used to model the MMP-1·THP interactions and develop a mechanism for the early stages of collagenolysis...
December 8, 2017: Journal of Physical Chemistry. B
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