| 1. |
- Moussa, Ehab, et al.
(author)
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Proteomic profiling of the brain of mice with experimental cerebral malaria
- 2018
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 180, s. 61-69
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Journal article (peer-reviewed)abstract
- Cerebral malaria (CM) is a severe neurological complication of malaria infection in both adults and children. In pursuit of effective treatment of CM, clinical studies, postmortem analysis and animal models have been employed to understand the pathology and identify effective interventions. In this study, a shotgun proteomics analysis was conducted to profile the proteomic signature of the brain tissue of mice with experimental cerebral malaria (ECM) in order to further understand the underlying pathology. To identify CM-associated response, proteomic signatures of the brains of C57/Bl6N mice infected with P. berghei ANKA that developed neurological syndrome were compared to those of mice infected with P. berghei NK65 that developed equally high parasite burdens without neurological signs, and to those of non-infected mice. The results show that the CM-associated response in mice that developed neurological signs comprise mainly acute-phase reaction and coagulation cascade activation, and indicate the leakage of plasma proteins into the brain parenchyma. SIGNIFICANCE: Cerebral malaria (CM) remains a major cause of death in children. The majority of these deaths occur in sub-Saharan Africa. Even with adequate access to treatment, mortality remains high and neurological sequelae can be found in up to 20% of survivors. No adjuvant treatment to date has been shown to reduce mortality and the pathophysiology of CM is largely unknown. Experimental cerebral malaria (ECM) is a well-established model that may contribute to identify and test druggable targets. In this study we have identified the disruption of the blood-brain barrier following inflammatory and vascular injury as a mechanism of disease. In this study we report a number of proteins that could be validated as potential biomarkers of ECM. Further studies, will be required to validate the clinical relevance of these biomarkers in human CM.
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| 2. |
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| 3. |
- Andersson, Björn, 1977, et al.
(author)
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Protein profiling identified dissociations between growth hormone-mediated longitudinal growth and bone mineralization in short prepubertal children
- 2011
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In: Journal of Proteomics. - : Elsevier BV. - 1876-7737 .- 1874-3919. ; 74:1, s. 89-100
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Journal article (peer-reviewed)abstract
- Growth hormone (GH) promotes longitudinal growth and bone mineralization. In this study, a proteomic approach was used to analyze the association between serum protein expression pattern and height-adjusted bone mineralization in short prepubertal children receiving GH treatment. Patterns of protein expression were compared with those associated with longitudinal bone growth. Specific protein expression patterns associated with changes in height-adjusted bone mineralization in response to GH treatment were identified. Out of the 37 peaks found in significant regression models, 27 were uniquely present in models correlated with changes in bone mineralization and 7 peaks were uniquely present in models correlated with changes in height. The peaks identified corresponded to apolipoproteins, transthyretin, serum amyloid A4 and hemoglobin beta. We conclude that a proteomic approach could be used to identify specific protein expression patterns associated with bone mineralization in response to GH treatment and that height-adjusted bone mineralization and longitudinal bone growth are regulated partly by the same and partly by different mechanisms. Protein isoforms with different post-translational modifications might be of importance in the regulation of these processes. However, further validation is needed to assess the clinical significance of the results.
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| 4. |
- Artemenko, Konstantin, et al.
(author)
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A proteomic approach to monitor the dynamic response of the female oviductal epithelial cell surface to male gametes
- 2015
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 113, s. 1-14
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Journal article (peer-reviewed)abstract
- UNLABELLED: Sophisticated strategies to analyze cell surface proteins are indispensable to study fundamental biological processes, such as the response of cells to environmental changes or cell-cell communication. Herein, we describe a refined mass spectrometry-based approach for the specific characterization and quantitation of cell surface proteins expressed in the female reproductive tract. The strategy is based on in situ biotinylation of rabbit oviducts, affinity enrichment of surface exposed biotin tagged proteins and dimethyl labeling of the obtained tryptic peptides followed by LC-MS/MS analysis. This approach proved to be sensitive enough to analyze small sample amounts (<1mug) and allowed further to trace the dynamic composition of the surface proteome of the oviductal epithelium in response to male gametes. The relative protein expression ratios of 175 proteins were quantified. Thirty-one of them were found to be altered over time, namely immediately, 1h and 2h after insemination compared to the time-matched control groups. Functional analysis demonstrated that structural reorganization of the oviductal epithelial cell surface was involved in the early response of the female organ to semen. In summary, this study outlines a workflow that is capable to monitor alterations in the female oviduct that are related to key reproductive processes in vivo. BIOLOGICAL SIGNIFICANCE: The proper interaction between the female reproductive tract, in particular, the oviduct and the male gametes, is fundamental to fertilization and embryonic development under physiological conditions. Thereby the oviductal epithelial cell surface proteins play an important role. Besides their direct interaction with male gametes, these molecules participate in signal transduction and, thus, are involved in the mandatory cellular response of the oviductal epithelium. In this study we present a refined LC-MS/MS based workflow that is capable to quantitatively analyze the expression of oviductal epithelial cell surface proteins in response to insemination in vivo. A special focus was on the very early interaction between the female organ and the male gametes. At first, this study clearly revealed an immediate response of the surface proteome to semen, which was modulated over time. The described methodology can be applied for studies of further distinct biological events in the oviduct and therefore contribute to a deeper insight into the formation of new life.
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| 5. |
- Azimzadeh, Omid, et al.
(author)
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Label-free protein profiling of formalin-fixed paraffin-embedded (FFPE) heart tissue reveals immediatemitochondrial impairment after ionising radiation
- 2012
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 75:8, s. 2384-2395
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Journal article (peer-reviewed)abstract
- Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics. However, quantitative proteome analysis of FFPE tissue is hampered by the lack of an efficient labelling method. The usage of conventional protein labelling on FFPE tissue has turned out to be inefficient. Classical labelling targets lysine residues that are blocked by the formalin treatment. The aim of this study was to establish a quantitative proteomics analysis of FFPE tissue by combining the label-free approach with optimised protein extraction and separation conditions. As a model system we used FFPE heart tissue of control and exposed C57BL/6 mice after total body irradiation using a gamma ray dose of 3 gray. We identified 32 deregulated proteins (p <= 0.05) in irradiated hearts 24 h after the exposure. The proteomics data were further evaluated and validated by bioinformatics and immunoblotting investigation. In good agreement with our previous results using fresh-frozen tissue, the analysis indicated radiation-induced alterations in three main biological pathways: respiratory chain, lipid metabolism and pyruvate metabolism. The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives.
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| 6. |
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| 7. |
- Bayram, Helen L., et al.
(author)
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Cross-species proteomics in analysis of mammalian sperm proteins
- 2016
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 135, s. 38-50
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Journal article (peer-reviewed)abstract
- Many proteomics studies are conducted in model organisms for which fully annotated, detailed, high quality proteomes are available. By contrast, many studies in ecology and evolution are conducted in species which lack high quality proteome data, limiting the perceived value of a proteomic approach for protein discovery and quantification. This is particularly true of rapidly evolving proteins in the reproductive system, such as those that have an immune function or are under sexual selection, and can compromise the potential for cross-species proteomics to yield confident identification. In this investigation we analysed the sperm proteome, from a range of ungulates and rodents, and explored the potential of routine proteomic workflows to yield characterisation and quantification in non-model organisms. We report that database searching is robust to cross-species matching for a mammalian core sperm proteome, comprising 623 proteins that were common to most of the 19 species studied here, suggesting that these proteins are likely to be present and identifiable across many mammalian sperm. Further, label-free quantification reveals a consistent pattern of expression level. Functional analysis of this core proteome suggests consistency with previous studies limited to model organisms and has value as a quantitative reference for analysis of species-specific protein characterisation.Significance: From analysis of the sperm proteome for diverse species (rodents and ungulates) using LC-MS/MS workflows and standard data processing, we show that it is feasible to obtain cross-species matches for a large number of proteins that can be filtered stringently to yield a highly expressed mammalian sperm core proteome, for which label-free quantitative data are also used to inform protein function and abundance.
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| 8. |
- Bespyatykh, Julia, et al.
(author)
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Proteogenomic analysis of Mycobacterium tuberculosis Beijing B0/W148 cluster strains
- 2019
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 192, s. 18-26
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Journal article (peer-reviewed)abstract
- Nowadays proteomics is one of the major instruments for editing and correcting annotation of genomic information. The correct genome annotation is necessary for omics studies of clinically relevant pathogens like Mycobacterium tuberculosis as well as for the progress in drug design and in silico biology. Here, we focused on the proteogenomic analysis of W-148 strain belonging to the Beijing B0/W148 cluster. This cluster, also known as a "successful" clone possesses unique pathogenic properties and has a unique genome organization. Taking into account high similarity of cluster strains at the genomic level we analyzed MS/MS dataset obtained for 63 clinical isolates of Beijing B0/W148. Based on H37Rv and W-148 annotations we identified 2546 proteins representing more than 60% of total proteome. A set of peptides (n = 404) specific for W-148 was found when compared with H37Rv. Start sites for 32 genes were corrected based on the combination of LC-MS/MS proteomic data with genomic six-frame translation. Additionally, we have shown the presence of peptides related to 10 genes earlier known as "pseudogenes". SIGNIFICANCE: Mycobacterium tuberculosis is one of the most dangerous pathogens. Phylogenetically, it may be divided into major lineages and among them, lineage 2 (predominantly Beijing genotype) one of the most successful lineages with an increasing prevalence in the global population. At the same time, strains of the Beijing B0/W148 cluster, a "successful" clone of Mycobacterium tuberculosis possess even more interesting features. Only one complete genome of this cluster, W-148, present in the NCBI database (CP012090.1) and it demonstrates a number of significant differences from the well-known reference genome H37Rv. For the W-148 strain many genes are annotated as "pseudo" and no attempts were made to correct this. Thereby, in this study, we have conducted a proteomic analysis of the cluster strains and corrected current genome annotation. We hope that the data obtained will help to increase the quality of identifications in proteomic and transcriptomic analysis of M. tuberculosis Beijing B0/W148 cluster strain in subsequent studies.
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| 9. |
- Bozaykut, Perinur, et al.
(author)
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The role of heat stress on the age related protein carbonylation
- 2013
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 89, s. 238-254
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Journal article (peer-reviewed)abstract
- Since the proteins are involved in many physiological processes in the organisms, modifications of proteins have important outcomes. Protein modifications are classified in several ways and oxidative stress related ones take a wide place. Aging is characterized by the accumulation of oxidized proteins and decreased degradation of these proteins. On the other hand protein turnover is an important regulatory mechanism for the control of protein homeostasis. Heat shock proteins are a highly conserved family of proteins in the various cells and organisms whose expressions are highly inducible during stress conditions. These proteins participate in protein assembly, trafficking, degradation and therefore play important role in protein turnover. Although the entire functions of each heat shock protein are still not completely investigated, these proteins have been implicated in the processes of protection and repair of stress-induced protein damage. This study has focused on the heat stress related carbonylated proteins, as a marker of oxidative protein modification, in young and senescent fibroblasts. The results are discussed with reference to potential involvement of induced heat shock proteins. This article is part of a Special Issue entitled: Protein Modifications. Biological significance Age-related protein modifications, especially protein carbonylation take a wide place in the literature. In this direction, to highlight the role of heat shock proteins in the oxidative modifications may bring a new aspect to the literature. On the other hand, identified carbonylated proteins in this study confirm the importance of folding process in the mitochondria which will be further analyzed in detail.
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| 10. |
- Brinkmalm-Westman, Ann, 1966, et al.
(author)
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SILAC zebrafish for quantitative analysis of protein turnover and tissue regeneration.
- 2011
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In: Journal of proteomics. - : Elsevier BV. - 1876-7737 .- 1874-3919. ; 75:2, s. 425-34
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Journal article (peer-reviewed)abstract
- Defective tissue regeneration is thought to contribute to several human diseases, including neurodegenerative disorders, heart failure and various lung diseases. Boosting the regenerative capacity has been suggested a possible therapeutic approach. Methods to metabolically label newly synthesized proteins in vivo with stable isotopic forms of amino acids holds promise for the study of protein turnover and tissue regeneration that are fundamental to the sustained life of all organisms. Here, we used the "stable isotope labeling with amino acids in cell culture" (SILAC) approach to explore normal protein turnover and tissue regeneration in adult zebrafish. The ratio of labeled and unlabeled proteins/peptides in specific organs of zebrafish fed a SILAC diet containing (13)C(6)-labeled lysine was determined by liquid chromatography and tandem mass spectrometry. Labeling was highest in tissues with high regenerative capacity, including intestine, liver, and fin, whereas brain and heart displayed the lowest labeling. Proteins with high degree of labeling were mainly involved in catalytic or transport activity pathways. The technique also verified increased protein synthesis during regeneration of the caudal fin following amputation. This newly developed SILAC zebrafish model constitutes a novel tool to analyze tissue regeneration in an animal model amenable to genetic and pharmacologic manipulation.
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| 11. |
- Budczies, Jan, et al.
(author)
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Comparative metabolomics of estrogen receptor positive and estrogen receptor negative breast cancer : alterations in glutamine and beta-alanine metabolism
- 2013
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In: Journal of Proteomics. - : Lippincott Williams & Wilkins. - 1874-3919 .- 1876-7737. ; 94, s. 279-288
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Journal article (peer-reviewed)abstract
- UNLABELLED: Molecular subtyping of breast cancer is necessary for therapy selection and mandatory for all breast cancer patients. Metabolic alterations are considered a hallmark of cancer and several metabolic drugs are currently being investigated in clinical trials. However, the dependence of metabolic alterations on breast cancer subtypes has not been investigated on -omics scale. Thus, 204 estrogen receptor positive (ER+) and 67 estrogen receptor negative (ER-) breast cancer tissues were investigated using GC-TOFMS based metabolomics. 19 metabolites were detected as altered in a predefined training set (2/3 of tumors) and could be validated in a predefined validation set (1/3 of tumors). The metabolite changes included increases in beta-alanine, 2-hydroyglutarate, glutamate, xanthine and decreases in glutamine in the ER- subtype. Beta-alanine demonstrated the strongest change between ER- and ER+ breast cancer (fold change=2.4, p=1.5E-20). In a correlation analysis with genome-wide expression data in a subcohort of 154 tumors, we found a strong negative correlation (Spearman R=-0.62) between beta-alanine and 4-aminobutyrate aminotransferase (ABAT). Immunohistological analysis confirmed down-regulation of the ABAT protein in ER- breast cancer. In a Kaplan-Meier analysis of a large external expression data set, the ABAT transcript was demonstrated to be a positive prognostic marker for breast cancer (HR=0.6, p=3.2E-15).BIOLOGICAL SIGNIFICANCE: It is well-known for more than a decade that breast cancer exhibits distinct gene expression patterns depending on the molecular subtype defined by estrogen receptor (ER) and HER2 status. Here, we show that breast cancer exhibits distinct metabolomics patterns depending on ER status. Our observation supports the current view of ER+ breast cancer and ER- breast as different diseases requiring different treatment strategies. Metabolic drugs for cancer including glutaminase inhibitors are currently under development and tested in clinical trials. We found glutamate enriched and glutamine reduced in ER- breast cancer compared to ER+ breast cancer and compared to normal breast tissues. Thus, metabolomics analysis highlights the ER- subtype as a preferential target for glutaminase inhibitors. For the first time, we report on a regulation of beta-alanine catabolism in cancer. In breast cancer, ABAT transcript expression was variable and correlated with ER status. Low ABAT transcript expression was associated with low ABAT protein expression and high beta-alanine concentration. In a large external microarray cohort, low ABAT expression shortened recurrence-free survival in breast cancer, ER+ breast cancer and ER- breast cancer.
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| 12. |
- Campos, Alexandre, et al.
(author)
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Proteomic research in bivalves Towards the identification of molecular markers of aquatic pollution
- 2012
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In: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 75:14, s. 4346-4359
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Research review (peer-reviewed)abstract
- Biomonitoring of aquatic environment and assessment of ecosystem health play essential roles in the development of effective strategies for the protection of the environment, human health and sustainable development. Biomarkers of pollution exposure have been extensively utilized in the last few decades to monitor the health of organisms and hence assess environmental status. However, the use of single biomarkers against biotic or abiotic stressors may be limited by the lack of sensitivity and specificity. Therefore, more recently, the search for novel biomarkers has been focused on the application of OMICS methodologies. Environmental proteomics focuses on the analysis of an organisms proteome and the detection of changes in the level of individual proteins/peptides in response to environmental stressors. Proteomics can provide a more robust approach for the assessment of environmental stress and therefore exposure to pollutants. This review aims to summarize the proteomic research in bivalves, a group of sessile and filter feeding organisms that play an important function as "sentinels" of the aquatic environment. A description of the main proteomic methodologies is provided. The current knowledge in bivalves toxicology, achieved with proteomics, is reported describing the main biochemical markers identified. A brief discussion regarding future challenges in this area of research emphasizing the development of more descriptive gene/protein databases that could support the OMICs approaches is presented. less thanbrgreater than less thanbrgreater thanThis article is part of a Special Issue entitled: Farm animal proteomics.
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| 13. |
- Campos, Alexandre, et al.
(author)
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Shotgun proteomics to unravel marine mussel (Mytilus edulis) response to long-term exposure to low salinity and propranolol in a Baltic Sea microcosm
- 2016
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In: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 137, s. 97-106
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Journal article (peer-reviewed)abstract
- Pharmaceuticals, among them the β-adrenoreceptor blocker propranolol, are an important group of environmental contaminants reported in European waters. Laboratory exposure to pharmaceuticals on marine species has been performed without considering the input of the ecosystem flow. To unravel the ecosystem response to long-term exposure to propranolol we have performed long-term exposure to propranolol and low salinity in microcosms. We applied shotgun proteomic analysis to gills of Mytilus edulis from those Baltic Sea microcosms and identified 2071 proteins with a proteogenomic strategy. The proteome profiling patterns from the 587 highly reproductive proteins among groups define salinity as a key factor in the mussel´s response to propranolol. Exposure at low salinity drives molecular mechanisms of adaptation based on a decrease in the abundance of several cytoskeletal proteins, signalling and intracellular membrane trafficking pathway combined with a response towards the maintenance of transcription and translation. The exposure to propranolol combined with low salinity modulates the expression of structural proteins including cilia functions and decrease the expression membrane protein transporters. This study reinforces the environment concerns of the impact of low salinity in combination with anthropogenic pollutants and anticipate critical physiological conditions for the survival of the blue mussel in the northern areas.
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| 14. |
- Cavanagh, Jorunn Pauline, et al.
(author)
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Comparative exoproteome profiling of an invasive and a commensal Staphylococcus haemolyticus isolate
- 2019
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In: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 197, s. 106-114
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Journal article (peer-reviewed)abstract
- Staphylococcus haemolyticus is a skin commensal emerging as an opportunistic pathogen. Nosocomial isolates of S. haemolyticus are the most antibiotic resistant members of the coagulase negative staphylococci (CoNS), but information about other S. haemolyticus virulence factors is scarce. Bacterial membrane vesicles (MVs) are one mediator of virulence by enabling secretion and long distance delivery of bacterial effector molecules while protecting the cargo from proteolytic degradation from the environment. We wanted to determine if the MV protein cargo of S. haemolyticus is strain specific and enriched in certain MV associated proteins compared to the totalsecretome.The present study shows that both clinical and commensal S. haemolyticus isolates produce membrane vesicles. The MV cargo of both strains was enriched in proteins involved in adhesion and acquisition of iron. The MV cargo of the clinical strain was further enriched in antimicrobial resistance proteins.Data are available via ProteomeXchange with identifier PXD010389.Biological significance: Clinical isolates of Staphylococcus haemolyticus are usually multidrug resistant, their main virulence factor is formation of biofilms, both factors leading to infections that are difficult to treat. We show that both clinical and commensal S. haemolyticusisolates produce membrane vesicles. Identification of staphylococcal membrane vesicles can potentially be used in novel approaches to combat staphylococcal infections, such as development of vaccines.
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| 15. |
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| 16. |
- Colomé, Núria, et al.
(author)
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Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis
- 2022
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In: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 251
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Journal article (peer-reviewed)abstract
- Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.
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| 17. |
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| 18. |
- de Wit, Meike, et al.
(author)
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Colorectal cancer candidate biomarkers identified by tissue secretome proteome profiling
- 2014
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 99, s. 26-39
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a major health problem. Biomarkers associated with molecular changes in cancer cells can aid early detection, diagnosis, prognosis, therapy selection, and disease monitoring. Tumor tissue secretomes are a rich source of candidate biomarkers. To identify CRC protein biomarkers, secretomes of four pairs of human CRC tissue and patient-matched normal colon tissue samples, and secretomes of five CRC cell lines were analyzed by GeLC-MS/MS. Subsequent data analysis was based on label-free spectral counting, Ingenuity Pathway Analysis, Secretome/SignalP, STRING and Cytoscape, resulting in 2703 protein identifications in the tissue secretomes, of which 409 proteins were significantly more present in CRC samples than in controls. Biomarker selection of 76 candidates was based on consistent and abundant over-representation in cancer-compared to control-secretomes, and presumed neoplastic origin. Overlap analysis with previously obtained datasets revealed 21 biomarkers suited for early detection of CRC. Immunohistochemistry confirmed overexpression in CRC of one candidate marker (MCM5). In conclusion, a human reference dataset of 76 candidate biomarkers was identified for which we illustrate that combination with existing pre-clinical datasets allows pre-selection of biomarkers for blood- or stool-based assays to support clinical management of CRC. Further dedicated validation studies are required to demonstrate their clinical applicability. Biological significance Tissue secretome proteomes are a rich source of candidate biomarkers. Several secretome proteome datasets have been obtained from pre-clinical in vitro and in vivo colorectal cancer (CRC) model systems, yielding promising CRC biomarkers obtained under well-defined experimentally controlled conditions. However, which of these biomarker proteins are actually secreted by human CRC samples was not known. To our knowledge, this is the first study that directly compares secretome proteomes from clinically relevant human CRC tissues to patient-matched normal colon tissues. We identified 76 human CRC protein biomarkers that may facilitate blood-based or stool-based assay development to support clinical management of CRC. Overlap analysis with datasets from well-defined pre-clinical studies helps to determine what clinical application suits these human CRC biomarkers best, i.e. early detection, diagnosis, prognosis, therapy selection, and/or disease monitoring of CRC. This is demonstrated for a CRC mouse model dataset, revealing 21 human CRC biomarkers suited for early detection of CRC.
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| 19. |
- Elf, Kristin, et al.
(author)
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Alterations in muscle proteome of patients diagnosed with amyotrophic lateral sclerosis
- 2014
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 108, s. 55-64
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive muscle paralysis. Currently clinical tools for ALS diagnostics do not perform well enough and their improvement is needed. The objective of this study was to identify specific protein alterations related to the development of ALS using tiny muscle biopsies. We applied a shotgun proteomics and quantitative dimethyl labeling in order to analyze the global changes in human skeletal muscle proteome of ALS versus healthy subjects for the first time. 235 proteins were quantified and 11 proteins were found significantly regulated in ALS muscles. These proteins are involved in muscle development and contraction, metabolic processes, enzyme activity, regulation of apoptosis and transport activity. In order to eliminate a risk to confuse ALS with other denervations, muscle biopsies of patients with postpolio syndrome and Charcot Marie Tooth disease (negative controls) were compared to those of ALS and controls. Only few proteins significantly regulated in ALS patients compared to controls were affected differently in negative controls. These proteins (BTB and kelch domain-containing protein 10, myosin light chain 3, glycogen debranching enzyme, transitional endoplasmic reticulum ATPase), individually or as a panel, could be selected for estimation of ALS diagnosis and development. Biological significance ALS is a devastating neurodegenerative disease, and luckily, very rare: only one to two people out of 100,000 develop ALS yearly. This fact, however, makes studies of ALS very challenging since it is very difficult to collect the representative set of clinical samples and this may take up to several years. In this study we collected the muscle biopsies from 12 ALS patients and compared the ALS muscle proteome against the one from control subjects. We suggested the efficient method for such comprehensive quantitative analysis by LC-MS and performed it for the first time using human ALS material. This gel- and antibody-free method can be widely applied for muscle proteome studies and has been used by us for revealing of the specific protein alterations associated with ALS.
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| 20. |
- Emami Khoonsari, Payam, et al.
(author)
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Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients
- 2019
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; , s. 35-43
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Journal article (peer-reviewed)abstract
- Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome. Based on our multivariate and univariate analyses, we found that the relative differences in the CSF proteome between FM patients and controls were moderate. Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.
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| 21. |
- Emami Khoonsari, Payam, et al.
(author)
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The human CSF pain proteome
- 2019
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In: Journal of Proteomics. - : ELSEVIER SCIENCE BV. - 1874-3919 .- 1876-7737. ; 190, s. 67-76
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Journal article (peer-reviewed)abstract
- Chronic pain represents one of the major medical challenges in the 21st century, affecting > 1.5 billion of the world population. Overlapping and heterogenous symptoms of various chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms. We have here investigated proteins found in human CSF with respect to known "pain" genes and in a cohort of patients with dysfunctional pain (fibromyalgia, FM), inflammatory pain (rheumatoid arthritis patients, RA) and non-pain controls utilized semi-quantitative proteomics using mass spectrometry (MS) to explore quantitative differences between these cohorts of patients. We found that "pain proteins" detected in CSF using MS are typically related to synaptic transmission, inflammatory responses, neuropeptide signaling- and hormonal activity. In addition, we found ten proteins potentially associated with chronic pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulin-dependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins might be of importance for understanding the mechanisms of dysfunctional/inflammatory chronic pain and also for use as potential biomarkers. Significance: Chronic pain is a common disease and it poses a large burden on worldwide health. Fibromyalgia (FM) is a heterogeneous disease of unknown etiology characterized by chronic widespread pain (CWP). The diagnosis and treatment of FM is based on the analysis of clinical assessments and no measurable biomarkers are available. Cerebrospinal fluid (CSF) has been historically considered as a rich source of biomarkers for diseases of nervous system including chronic pain. Here, we explore CSF proteome of FM patients utilizing mass spectrometry based quantitative proteomics method combined with multivariate data analysis in order to monitor the dynamics of the CSF proteome. Our findings in this exploratory study support notable presence of pain related proteins in CSF yet with specific domains including inflammatory responses, neuropeptide signaling- and hormonal activity. We have investigated molecular functions of significantly altered proteins and demonstrate presence of 176 known pain related proteins in CSF. In addition, we found ten proteins potentially associated with pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulindependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins are novel in the context of FM but are known to be involved in pain mechanisms including inflammatory response and signal transduction. These results should be of clear significance and interest for researchers and clinicians working in the field of pain utilizing human CSF and MS based proteomics.
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| 22. |
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| 23. |
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| 24. |
- Gonzalez, Henrik, et al.
(author)
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Identification of novel candidate protein biomarkers for the post-polio syndrome — Implications for diagnosis, neurodegeneration and neuroinflammation
- 2009
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 71:6, s. 670-681
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Journal article (peer-reviewed)abstract
- Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS displayed a disease-specific and highly predictive (p=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients.
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- Goodwin, Richard J. A., et al.
(author)
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Conductive carbon tape used for support and mounting of both whole animal and fragile heat-treated tissue sections for MALDI MS imaging and quantitation
- 2012
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In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 75:16, s. 4912-4920
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Journal article (peer-reviewed)abstract
- Analysis of whole animal tissue sections by MALDI MS imaging (MSI) requires effective sample collection and transfer methods to allow the highest quality of in situ analysis of small or hard to dissect tissues. We report on the use of double-sided adhesive conductive carbon tape during whole adult rat tissue sectioning of carboxymethyl cellulose (CMC) embedded animals, with samples mounted onto large format conductive glass and conductive plastic MALDI targets, enabling MSI analysis to be performed on both TOF and FT-ICR MALDI mass spectrometers. We show that mounting does not unduly affect small molecule MSI detection by analyzing tiotropium abundance and distribution in rat lung tissues, with direct on-tissue quantitation achieved. Significantly, we use the adhesive tape to provide support to embedded delicate heat-stabilized tissues, enabling sectioning and mounting to be performed that maintained tissue integrity on samples that had previously been impossible to adequately prepare section for MSI analysis. The mapping of larger peptidomic molecules was not hindered by tape mounting samples and we demonstrate this by mapping the distribution of PEP-19 in both native and heat-stabilized rat brains. Furthermore, we show that without heat stabilization PEP-19 degradation fragments can detected and identified directly by MALDI MSI analysis.This article is part of a Special Issue entitled: Imaging Mass Spectrometry: A User's Guide to a New Technique for Biological and Biomedical Research.
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