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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...
October 12, 2016: Journal of Pharmaceutical and Biomedical Analysis
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
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
Miloslav Sanda, Julius Benicky, Jing Wu, Yiwen Wang, Kepher Makambi, Jaeil Ahn, Coleman I Smith, Peng Zhao, Lihua Zhang, Radoslav Goldman
BACKGROUND: Non-invasive monitoring of liver disease remains an important health issue. Liver secreted glycoproteins reflect pathophysiological states of the organ and represent a rational target for serologic monitoring. In this study, we describe sialylated O-glycoforms of liver-secreted hemopexin (HPX) and quantify them as a ratio of disialylated to monosialylated form (S-HPX). METHODS: We measured S-HPX in serum of participants of the HALT-C trial using a LC-MS/MS-MRM assay...
2016: Clinical Proteomics
Mark A Baker, Elena K Schneider, Johnny X Huang, Matthew A Cooper, Jian Li, Tony Velkov
Ertapenem is an important first-line carbapenem antibiotic used for the treatment of aerobic Gram-negative bacterial infections. It is the only carbapenem that is highly bound to plasma proteins and displays a concentration-dependent and saturable plasma protein binding profile. To date the plasma components responsible for sequestering ertapenems antibacterial activity remain uncharacterised. In the present study we have employed an orthogonal, multi-platform approach, including novel compound-centric displacement proteomics and Surface Plasmon Resonance to characterise the plasma protein binding proteome of ertapenem...
September 28, 2016: ACS Chemical Biology
Dan Gao, Ning Qiu, Yaping Liu, Meihu Ma
BACKGROUND: Physical changes such as chicken egg white thinning and flattening of egg yolk occur during storage, implying the decline of the egg qualities. To reveal the deteriorative process related to the chicken egg internal qualities, comparative proteomic method was used in this study to analyze the alterations of egg yolk plasma proteins at different storage times (0, 20, and 40 days) under ambient temperature of 22 ± 2 °C. RESULT: Using two-dimensional electrophoresis (2-DE) followed by MALDI-TOF MS/MS, 33 protein spots representing 12 proteins were identified with significant (p ˂ 0...
September 24, 2016: Journal of the Science of Food and Agriculture
Petra Darebna, Petr Novak, Radek Kucera, Ondrej Topolcan, Miloslav Sanda, Radoslav Goldman, Petr Pompach
: Alternations in the glycosylation of proteins have been described in connection with several cancers, including hepatocellular carcinoma (HCC) and colorectal cancer. Analytical tools, which use combination of liquid chromatography and mass spectrometry, allow precise and sensitive description of these changes. In this study, we use MRM and FT-ICR operating in full-MS scan, to determine ratios of intensities of specific glycopeptides in HCC, colorectal cancer, and liver metastasis of colorectal cancer...
September 16, 2016: Journal of Proteomics
Z Yilmaz, O Eralp Inan, M Kocaturk, A T Baykal, O Hacariz, I Hatipoglu, A Tvarijonaviciute, M Cansev, J Ceron, I H Ulus
BACKGROUND: This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics. These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical situation. METHODS: Healthy-calves (n = 20) were divided into 4 groups: Control, Choline treated (C), Lipopolysaccharide administered (LPS), and LPS + C...
2016: BMC Veterinary Research
Tigist Kassa, Sirsendu Jana, Fantao Meng, Abdu I Alayash
Despite advances in our understanding of the oxidative pathways mediated by free hemoglobin (Hb), the precise contribution of its highly reactive redox forms to tissue and organ toxicities remains ambiguous. Heme, a key degradation byproduct of Hb oxidation, has recently been recognized as a damage-associated molecular pattern (DAMP) molecule, able to trigger inflammatory responses. Equally damaging is the interaction of the highly redox active forms of Hb with other biological molecules. We determined the kinetics of heme loss from individual Hb redox states-ferrous (Fe(2+)), ferric (Fe(3+)), and ferryl (Fe(4+))-using two different heme receptor proteins: hemopexin (Hxp), a naturally occurring heme scavenger in plasma, and a double mutant (H64Y/V86F), apomyoglobin (ApoMb), which avidly binds heme released from Hb...
September 2016: FEBS Open Bio
Lucas Delmonico, Maryah Bravo, Rafaele Tavares Silvestre, Maria Helena Faria Ornellas, Carolina Maria De Azevedo, Gilda Alves
The present study evaluated the proteomic profile of saliva and plasma from women with impalpable breast lesions using nano-liquid chromatography-quadrupole-time-of-flight (nLC-Q-TOF) technology. Plasma and saliva from patients with fibroadenoma (n=10), infiltrating ductal carcinoma (n=10) and healthy control groups (n=8) were assessed by combinations of inter/intra-group analyses, revealing significant quantitative and qualitative differences. The major differentially-expressed proteins in the saliva of patients compared with the controls were α2-macroglobulin and ceruloplasmin, but the proteins that met the minimum fold-change and P-value cut-offs were leukocyte elastase inhibitor and α-enolase, and deleted in malignant brain tumors 1...
September 2016: Oncology Letters
Rosaria Viola Abbritti, Francesca Polito, Maria Cucinotta, Claudio Lo Giudice, Maria Caffo, Chiara Tomasello, Antonino Germanò, Mohammed Aguennouz
Meningiomas are one of the most common tumors affecting the central nervous system, exhibiting a great heterogeneity in grading, treatment and molecular background. This article provides an overview of the current literature regarding the molecular aspect of meningiomas. Analysis of potential biomarkers in serum, cerebrospinal fluid (CSF) and pathological tissues was reported. Applying bioinformatic methods and matching the common proteic profile, arising from different biological samples, we highlighted the role of nine proteins, particularly related to tumorigenesis and grading of meningiomas: serpin peptidase inhibitor alpha 1, ceruloplasmin, hemopexin, albumin, C3, apolipoprotein, haptoglobin, amyloid-P-component serum and alpha-1-beta-glycoprotein...
September 2016: Cancer Genomics & Proteomics
Robyn E Elphinstone, Andrea L Conroy, Michael Hawkes, Laura Hermann, Sophie Namasopo, H Shaw Warren, Chandy C John, W Conrad Liles, Kevin C Kain
BACKGROUND: Malaria remains a major cause of global mortality. Extracellular heme, released during malaria-induced hemolysis, mediates a number of pathogenic processes associated with vascular and organ injury. Hemopexin (hpx) facilitates the degradation of extracellular heme. In this study, we explore the hypothesis that dysregulation of the heme-hpx axis is associated with disease severity, acute kidney injury (AKI), and outcome. METHODS: Plasma levels of hemin and hpx (at admission, day 3, and day 14) were assessed in children with severe malaria in Jinja, Uganda...
October 15, 2016: Journal of Infectious Diseases
Jan A Graw, Claire Mayeur, Ivy Rosales, Yumin Liu, Venkata S Sabbisetti, Frank E Riley, Osher Rechester, Rajeev Malhotra, H Shaw Warren, Robert B Colvin, Joseph V Bonventre, Donald B Bloch, Warren M Zapol
BACKGROUND: Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme...
September 27, 2016: Circulation
Suzanne Miyamoto, L Renee Ruhaak, Carol Stroble, Michelle R Salemi, Brett Phinney, Carlito B Lebrilla, Gary S Leiserowitz
Ovarian cancer is a major cause of cancer mortality among women, largely due to late diagnosis of advanced metastatic disease. More extensive molecular analysis of metastatic ovarian cancer is needed to identify post-translational modifications of proteins, especially glycosylation that is particularly associated with metastatic disease to better understand the metastatic process and identify potential therapeutic targets. Glycoproteins in ascites fluid were enriched by affinity binding to lectins (ConA or WGA) and other affinity matrices...
September 2, 2016: Journal of Proteome Research
Gregory M Vercellotti, Ping Zhang, Julia Nguyen, Fuad Abdulla, Chunsheng Chen, Phong Nguyen, Carlos Nowotny, Clifford J Steer, Ann Smith, John D Belcher
Sickle cell disease (SCD) patients have low serum hemopexin (Hpx) levels due to chronic hemolysis. We hypothesize that in SCD mice, hepatic overexpression of hemopexin will scavenge the proximal mediator of vascular activation, heme, and will inhibit inflammation and microvascular stasis. To examine the protective role of Hpx in SCD, we transplanted bone marrow from NY1DD SCD mice into Hpx(-/-) or Hpx(+/+) C57BL/6 mice. Dorsal skin fold chambers were implanted in week 13 post-transplant and microvascular stasis (% non-flowing venules) evaluated in response to heme infusion...
July 19, 2016: Molecular Medicine
Frederico Alisson-Silva, Kunio Kawanishi, Ajit Varki
One of the most consistent epidemiological associations between diet and human disease risk is the impact of red meat consumption (beef, pork, and lamb, particularly in processed forms). While risk estimates vary, associations are reported with all-cause mortality, colorectal and other carcinomas, atherosclerotic cardiovascular disease, type II diabetes, and possibly other inflammatory processes. There are many proposed explanations for these associations, some long discussed in the literature. Attempts to explain the effects of red meat consumption have invoked various red meat-associated agents, including saturated fat, high salt intake, Trimethylamine-N-oxide (TMAO) generation by microbiota, and environmental pollutants contaminating red meat, none of which are specific for red meat...
October 2016: Molecular Aspects of Medicine
Linda Cerofolini, Sabrina Amar, Janelle L Lauer, Tommaso Martelli, Marco Fragai, Claudio Luchinat, Gregg B Fields
Cell surface proteolysis is an integral yet poorly understood physiological process. The present study has examined how the pericellular collagenase membrane-type 1 matrix metalloproteinase (MT1-MMP) and membrane-mimicking environments interplay in substrate binding and processing. NMR derived structural models indicate that MT1-MMP transiently associates with bicelles and cells through distinct residues in blades III and IV of its hemopexin-like domain, while binding of collagen-like triple-helices occurs within blades I and II of this domain...
2016: Scientific Reports
Roopa Kothapalli, Kodappully Sivaraman Siveen, Tuan Zea Tan, Jean Paul Thiery, Alan Prem Kumar, Gautam Sethi, Kunchithapadam Swaminathan
Considering the pathological significance of MMP-13 in breast and colon cancers, exosite-based inhibition of the C-terminal hemopexin (Hpx) domain could serve as an alternative strategy to develop selective inhibitors for MMP-13.Two of six lead compounds, compound 5 (2,3-dihydro-1,4-benzodioxine-5-carboxylic acid) and compound 6 (1-acetyl-4-hydroxypyrrolidine-2-carboxylic acid) exhibited considerable inhibitory activity against MMP-13. Complementing to this study, we have also shown the gene expression levels of MMP-13 within the subtypes of colon and breast cancers classified from patients' tissue samples to provide a better understanding on which subtype of breast cancer patients would get benefited by MMP-13 inhibitors...
June 29, 2016: Bioscience, Biotechnology, and Biochemistry
Gaiqing Wang, Anatol Manaenko, Anwen Shao, Yibo Ou, Peng Yang, Enkhjargal Budbazar, Derek Nowrangi, John H Zhang, Jiping Tang
Heme-degradation after erythrocyte lysis plays an important role in the pathophysiology of intracerebral hemorrhage. Low-density lipoprotein receptor-related protein-1 is a receptor expressed predominately at the neurovascular interface, which facilitates the clearance of the hemopexin and heme complex. In the present study, we investigated the role of low-density lipoprotein receptor-related protein-1 in heme removal and neuroprotection in a mouse model of intracerebral hemorrhage. Endogenous low-density lipoprotein receptor-related protein-1 and hemopexin were increased in ipsilateral brain after intracerebral hemorrhage, accompanied by increased hemoglobin levels, brain water content, blood-brain barrier permeability and neurological deficits...
June 17, 2016: Journal of Cerebral Blood Flow and Metabolism
You Wu, Jianyong Tang, Chanjuan Zhou, Libo Zhao, Jin Chen, Li Zeng, Chenglong Rao, Haiyang Shi, Li Liao, Zihong Liang, Yongtao Yang, Jian Zhou, Peng Xie
Major depressive disorder (MDD) is a highly prevalent and debilitating mental illness with substantial impairments in quality of life and functioning. However, the pathophysiology of major depression remains poorly understood. Combining the brain and body should provide a comprehensive understanding of the etiology of MDD. As the largest internal organ of the human body, the liver has an important function, yet no proteomic study has assessed liver protein expression in a preclinical model of depression. Using the chronic unpredictable mild stress (CUMS) mouse model of depression, differential protein expression between CUMS and control (CON) mice was examined in the liver proteome using isobaric tag for relative and absolute quantitation (iTRAQ) coupled with tandem mass spectrometry...
September 15, 2016: Behavioural Brain Research
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