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At least 1,567 records · Page 87Linked to original sources
PubMed2005

"Coelionomics": towards understanding the molecular pathology of coeliac disease.

Coeliac disease (CD) is an inflammatory disorder of the small intestine characterised by a permanent intolerance to gluten-derived peptides. When gluten-derived peptides reach the lamina propria in CD patients, they provoke specific changes in the mucosa of their small intestine. Although the susceptibility to CD is strongly determined by environmental gluten, it is clearly a common genetic disorder. Important genetic factors for CD are the HLA-DQ genes located in the MHC region on chromosome 6 [HLA-DQ2 (95%) or HLA-DQ8 ( approximately 5%) heterodimers]. So far, the only treatment for CD consists of a life-long gluten-free diet. A key question in CD is why the gluten-derived peptides are resistant to further breakdown by endogenous proteases and how, in turn, they can activate a harmful immune response in the lamina propria of genetically predisposed individuals. Four mechanisms, namely apoptosis, oxidative stress, matrix metalloproteinases and dysregulation of proliferation and differentiation, are thought to play a role in the pathophysiology of CD. Whether the genes involved in these four mechanisms play a causative role in the development of the villous atrophy or are, in fact, a consequence of the disease process is unknown. In this review we summarise these mechanisms and discuss their validity in the context of current insights derived from genetic, genomic and molecular studies. We also discuss future directions for research and the therapeutic implications for patients.

Apoptosis↗
PubMed2001

Prediction of higher order functional networks from genomic data.

Post-genomics may be defined in different ways depending on how one views the challenges after the discovery of the genome. A traditional view is to follow the concept of the central dogma in molecular biology, namely from genome to transcriptome to proteome. Projects are ongoing to analyse gene expression profiles both at the mRNA and protein levels, and to catalogue protein 3D structure families, which will no doubt help the understanding of the information in the genome. However, once complete, such experimentally determined catalogues of genes, RNAs and proteins only tell us about the building blocks of life. They do not tell us much about how life operates as a system, such as higher order functional behaviours of the cell or the organism. Thus, an alternative view of post-genomics is to go up from the molecular level to the cellular level and eventually to still higher levels, i.e., the biological systems. Bioinformatics provides basic concepts as well as practical methods to integrate this view with the traditional view and to analyse complex interactions among building blocks and with dynamic environments.

Computational Biology↗
PubMed2004

GoSurfer: a graphical interactive tool for comparative analysis of large gene sets in Gene Ontology space.

UNLABELLED: The analysis of complex patterns of gene regulation is central to understanding the biology of cells, tissues and organisms. Patterns of gene regulation pertaining to specific biological processes can be revealed by a variety of experimental strategies, particularly microarrays and other highly parallel methods, which generate large datasets linking many genes. Although methods for detecting gene expression have improved substantially in recent years, understanding the physiological implications of complex patterns in gene expression data is a major challenge. This article presents GoSurfer, an easy-to-use graphical exploration tool with built-in statistical features that allow a rapid assessment of the biological functions represented in large gene sets. GoSurfer takes one or two list(s) of gene identifiers (Affymetrix probe set ID) as input and retrieves all the Gene Ontology (GO) terms associated with the input genes. GoSurfer visualises these GO terms in a hierarchical tree format. With GoSurfer, users can perform statistical tests to search for the GO terms that are enriched in the annotations of the input genes. These GO terms can be highlighted on the GO tree. Users can manipulate the GO tree in various ways and interactively query the genes associated with any GO term. The user-generated graphics can be saved as graphics files, and all the GO information related to the input genes can be exported as text files. AVAILABILITY: GoSurfer is a Windows-based program freely available for noncommercial use and can be downloaded at http://www.gosurfer.org. Datasets used to construct the trees shown in the figures in this article are available at http://www.gosurfer.org/download/GoSurfer.zip.

Computer Graphics↗
PubMed2003

A new tool for routine testing of cellular protein expression: integration of cell staining and analysis of protein expression on a microfluidic chip-based system.

The key benefits of Lab-on-a-Chip technology are substantial time savings via an automation of lab processes, and a reduction in sample and reagent volumes required to perform analysis. In this article we present a new implementation of cell assays on disposable microfluidic chips. The applications are based on the controlled movement of cells by pressure-driven flow in microfluidic channels and two-color fluorescence detection of single cells. This new technology allows for simple flow cytometric studies of cells in a microfluidic chip-based system. In addition, we developed staining procedures that work "on-chip," thus eliminating time-consuming washing steps. Cells and staining-reagents are loaded directly onto the microfluidic chip and analysis can start after a short incubation time. These procedures require only a fraction of the staining reagents generally needed for flow cytometry and only 30,000 cells per sample, demonstrating the advantages of microfluidic technology. The specific advantage of an on-chip staining reaction is the amount of time, cells, and reagents saved, which is of great importance when working with limited numbers of cells, e.g., primary cells or when needing to perform routine tests of cell cultures as a quality control step. Applications of this technology are antibody staining of proteins and determination of cell transfection efficiency by GFP expression. Results obtained with microfluidic chips, using standard cell lines and primary cells, show good correlation with data obtained using a conventional flow cytometer.

Antibodies↗
PubMedDate not supplied

Proteomics. Concepts and perspectives.

Within the last five years the field of proteomics has changed the understanding of molecular biology. Proteins manifest physiological as well as pathophysiological processes in a cell or an organism, and proteomics describes the complete protein inventory in dependence on in vivo parameters. Disease mechanism or drug effects both affect a protein profile and, vice versa, characterising protein profiles reveals information for the understanding of disease and therapy. Analytical methods for proteomics are based on conventional tools for protein characterisation. The technical challenge is the complete coverage of physico-chemical properties for thousands of proteins. Nucleic acids display a relative chemical homogeneity and therefore genomics was considered more promising in the past than proteomics. Further improvements in proteomics technologies will likely change this course with proteomics complementing genomics as a tool to study life sciences.

Animals↗
PubMed2001

Proteomic analysis of apoptosis initiation induced by all-trans retinoic acid in human acute promyelocytic leukemia cells.

The irreversible destiny of apoptosis in its early stage might play a critical role in the apoptosis of human acute promyelocytic leukemia (APL) cell line induced by all-trans retinoic acid (ATRA). To characterize protein alterations during the apoptosis-initiation phase and to understand the metabolic status at that time, we investigated the protein profiles in the apoptosis-initiation phase of APL cell line HL-60 by proteomic analysis. ATRA-withdrawal was conducted to demonstrate that there was committed initiation phase of apoptosis triggered by 10(-6) M ATRA at day 3. Only after that time point, ATRA-treated cells irreversibly went to apoptosis. Also at that time point, the positive regulators of apoptosis such as STAT3 increased at protein level, whereas negative regulators (Bcl-2 and p-STAT3) decreased. In addition, caspase-3 also increased after that time. Furthermore, comparative proteomic analysis was utilized to examine the protein expression profiles during the initiation stage of apoptosis. Our results showed 12 upregulated and 7 downregulated proteins experiencing twofold alteration, including key regulators of signal transduction such as G-proteins and nucleic receptors, proteins related with metabolism, oxidation and reduction, proteins associated with the nucleus and cytoskeleton-related proteins. Some of them could be positive modulators to trigger apoptosis, whereas others could contribute to intracellular defense against apoptosis induced by exogenous triggers. The results above suggest that there is a subtle balance between apoptosis and the intracellular defense against apoptosis. Once the balance is disturbed, cells would irreversibly initiate to undergo the execution of apoptosis.

Amino Acids↗
PubMed2006

Proteomic methods in nutrition.

PURPOSE OF REVIEW: Proteomics, the comprehensive analysis of a protein complement in a cell, tissue or biological fluid at a given time, is a key player in the family of -omic disciplines, which encompass genomics (gene analysis), transcriptomics (gene expression analysis) and metabolomics (metabolite profiling). This review summarizes the state of the art of proteomics technology and puts it into perspective for food-related research. Learning from proteomic experiences in the pharmaceutical context, this article may help to translate proteomics into nutrition and health. RECENT FINDINGS: Mass spectrometric technology has progressed enormously with regard to mass accuracy, resolution and peptide sequencing power. Likewise, upstream separation, depletion and enrichment techniques now allow us to deal with the large complexity and wide dynamic range of proteomic samples more efficiently. Consequently, proteomic studies now provide a broader, but still far from complete, coverage of a given proteome. SUMMARY: Proteomics adapted and applied to the context of nutrition and health has the potential to deliver biomarkers for health and comfort, reveal early indicators of disease disposition, assist in differentiating dietary responders from non-responders, and, last but not least, discover bioactive, beneficial food components.

Biomarkers↗
PubMed2007

Profiling of human mesangial cell subproteomes reveals a role for calmodulin in glucose uptake.

Proteomics combined with cell fractionation was used to identify proteins regulated by high glucose (HG) in human mesangial cells (HMC). Total membrane and cytosolic fraction proteins derived from HMC after 7 days of HG exposure were resolved by a two-dimensional gel electrophoresis approach. DeCyder software was used to analyze the HG-induced protein spot dysregulation. In the membrane subproteome, of the 92 spots that were matched across all gels, HG induced significant downregulation of only 4 protein spots. The dysregulated spots from the membrane subproteome included binding protein (BiP), calreticulin precursor protein, a 63-kDa transmembrane protein from a ER/Golgi intermediate, and beta-subunit of collagen proline 4-hydroxylase. In the cytosolic subproteome, of the 122 spots that were matched across all gels, HG induced downregulation of 3 protein spots and upregulation of 2 protein spots significantly. Enolase 1, annexin VI, and gamma(2)-actin were decreased, whereas heat shock protein-70 kDa and calmodulin (CaM) were increased. Further confocal microscopy and Western immunoblotting of mesangial cells validated the increase in CaM. Immunoblotting of diabetic mouse and rat kidneys exhibited a marked increase in CaM at both early and late stages of diabetes, reflecting the potential physiological relevance of CaM upregulation. CaM-specific inhibitors blocked glucose transport stimulated by transforming growth factor-beta and insulin in mesangial cells. In conclusion, using a combination of cell fractionation and protein expression profiling, we identified a cohort of HG-dysregulated proteins in the HMC and identified a critical and as yet unrecognized role for CaM in glucose transport in mesangial cells.

Animals↗
PubMed2004

The instantly released Drosophila immune proteome is infection-specific.

In this study, we analyzed the hemolymph proteome of Drosophila third instar larvae, which were induced with a suspension of Gram-positive bacteria or yeast. Profiling of the hemolymph proteins of infected versus non-infected larvae was performed by two-dimensional difference gel electrophoresis. Infection with Micrococcus luteus or Saccharomyces cerevisiae induced, respectively, 20 and 19 differential protein spots. The majority of the spots are specifically regulated by one pathogen, whereas only a few spots correspond to proteins altered in all cases of challenging (including after challenge with lipopolysaccharides). All of the upregulated proteins can be assigned to specific aspects of the immune system, as they did not increase in the hemolymph of sterile pricked larvae. Next to known immune proteins, unannotated proteins were identified such as CG4306 protein, which has homologues with unknown function in all metazoan genome databases available today.

Animals↗
PubMed2026

A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical-like and dopaminergic-like induced neurons.

Lysosomes maintain cellular homeostasis by degrading proteins delivered via endocytosis and autophagy and by recycling building blocks for organelle biogenesis. Lysosomal storage disorders (LSDs) comprise a group of diseases affecting diverse lysosomal functions. To facilitate molecular phenotyping across diverse LSD gene classes, we are developing a library of human embryonic stem cells engineered to lack individual LSD genes as a resource for the field. Here, we report our initial stem cell toolkit lacking one of 23 LSD genes, including the majority of genes associated with sphingolipidoses and neuronal ceroid lipofuscinoses, and its use in the generation of a proteomic resource for induced cortical-like and midbrain dopaminergic-like neurons. In-depth abundance and correlation profiling across organelles and suborganelle components revealed potential vulnerabilities that reflect distinct patterns of proteome alterations across both genotypes and neuronal cell types. We characterize alterations in the mitochondrial proteome associated with GBA1 and ASAH1 deficiency and identify synaptic and mitochondrial defects in ASAH1-/- induced neurons that correlate with defects in neuronal firing rates. Moreover, we developed an informatic pipeline for proteome-wide identification of individual protein-protein interactions and protein complexes that may be disrupted as a result of LSD gene deficiency. Finally, we visualized structural alterations of ASAH1-deficient endolysosomes in situ using cryoelectron tomography, revealing swollen organelles that were largely devoid of dense internal membranes characteristic of wild-type cells, but containing numerous intralumenal vesicle compartments. This toolkit and associated proteomic landscapes provide a resource for defining molecular signatures associated with LSD gene dysfunction and organelle vulnerability.

Humans↗
PubMed2005

Proteome alterations in gamma-irradiated human T-lymphocyte leukemia cells.

Analyses of the protein expression profiles of irradiated cells may be beneficial for identification of new biomolecules of radiation-induced cell damage. Therefore, in this study we exploited the proteomic approach to identify proteins whose expression is significantly altered in gamma-irradiated human T-lymphocyte leukemia cells. MOLT-4 cells were irradiated with 7.5 Gy and the cell lysates were collected at different times after irradiation (2, 5 and 12 h). The proteins were separated by two-dimensional electrophoresis and quantified using an image evaluation system. Proteins exhibiting significant radiation-induced alterations in abundance were identified by peptide mass fingerprinting. We identified 14 proteins that were either up- or down-regulated. Cellular levels of four of the proteins (Rho GDP dissociation inhibitor 1 and 2, Ran binding protein 1, serine/threonine protein kinase PAK2) were further analyzed by two-dimensional immunoblotting to confirm the data obtained from proteome analysis. All identified proteins were classified according to their cellular function, including their participation in biochemical and signaling pathways. Taken together, our results suggest the feasibility of the proteome method for monitoring of cellular radiation responses.

Cell Line, Tumor↗
PubMed2006

Proteomic-based prediction of clinical behavior in adult acute lymphoblastic leukemia.

BACKGROUND: Response in adult acute lymphoblastic leukemia (ALL) can be achieved in a majority of patients. However, unlike pediatric ALL, recurrence is common in adult ALL, and the ability to predict at an early stage which patients are most likely to experience recurrence may help in devising new therapeutic approaches to prevent recurrence. METHODS: Peripheral blood plasma from 57 patients with confirmed ALL was obtained before induction therapy for proteomic analysis. Follow-up continued for a median period of 71 weeks. For each plasma sample, 4 fractions eluted from a strong anion column were applied to 3 different ProteinChip array surfaces, and 12 surface-enhanced laser desorption/ionization (SELDI) spectra were generated. Peaks that correlated with recurrence were identified and decision trees were constructed and evaluated, using only 2 peaks per predictive tree. RESULTS: The best decision trees provided strong positive prediction of recurrence, with correct predictions 84% to 92% of the time, whereas negative prediction of patients who did not experience recurrence was less robust, with 62% to 74% accuracy. Prediction of recurrence was independent of cytogenetics, bone marrow blast count, lactate dehydrogenase, beta-2-microglobulin, or surface markers. Positive prediction of L3 morphological classification was achieved in 80% of test cases. CONCLUSIONS: Peripheral blood plasma is adequate to predict clinical behavior in ALL patients irrespective of the percentage of bone marrow blasts. Proteomic analysis of plasma offers a useful approach for profiling patients with ALL.

Adolescent↗
PubMed2002

Targeting of tumor associated antigens in renal cell carcinoma using proteome-based analysis and their clinical significance.

The suitability of proteome-based strategies for the targeting of tumor-associated markers along with further analysis regarding their clinical significance were investigated in human renal cell carcinoma (RCC). The immunogenic protein expression profile of normal kidney and RCC cell lines was studied by proteome analysis combined with immunoblotting using sera from healthy donors and RCC patients, also termed PROTEOMEX. Employing this approach, a series of proteins reactive with either RCC patient sera and/or reactive with control sera were identified by microanalysis of tryptic peptides. Some of these candidate antigens represent members of the cytoskeletal family, such as cytokeratins, in particular cytokeratin 8, cytoskeletal tropomyosin, F-actin capping protein, gamma-actin, stathmin, tubulin-alpha, tubulin-beta and vimentin. The expression pattern and clinical significance of three of these antigens, namely cytokeratin 8, stathmin and vimentin, were further analyzed in a large series of surgically removed RCC lesions of distinct subtypes. A heterogeneous expression pattern of cytokeratin 8, stathmin and vimentin was demonstrated in the different RCC subtypes. All epithelial cells of the autologous normal kidney showed a strong cytokeratin 8 staining pattern, whereas they totally lack vimentin expression. Stathmin was expressed in 10% of tubule cells. In conclusion, PROTEOMEX could be employed for the identification of tumor-associated antigens of the cytoskeleton which are differentially expressed in RCC of distinct subtypes as well as in normal renal epithelium.

Antigens, Neoplasm↗
PubMed2006

Quantitative proteomic analysis of the budding yeast cell cycle using acid-cleavable isotope-coded affinity tag reagents.

Quantitative profiling of proteins, the direct effectors of nearly all biological functions, will undoubtedly complement technologies for the measurement of mRNA. Systematic proteomic measurement of the cell cycle is now possible by using stable isotopic labeling with isotope-coded affinity tag reagents and software tools for high-throughput analysis of LC-MS/MS data. We provide here the first such study achieving quantitative, global proteomic measurement of a time-course gene expression experiment in a model eukaryote, the budding yeast Saccharomyces cerevisiae, during the cell cycle. We sampled 48% of all predicted ORFs, and provide the data, including identifications, quantitations, and statistical measures of certainty, to the community in a sortable matrix. We do not detect significant concordance in the dynamics of the system over the time-course tested between our proteomic measurements and microarray measures collected from similarly treated yeast cultures. Our proteomic dataset therefore provides a necessary and complementary measure of eukaryotic gene expression, establishes a rich database for the functional analysis of S. cerevisiae proteins, and will enable further development of technologies for global proteomic analysis of higher eukaryotes.

Carbon Isotopes↗
PubMed2026

Imaging-Guided Omics Technologies for Resolving Rare Cancer States and Advancing Nanomedicine.

The ability to resolve rare and transient cellular states is critical for understanding metastasis, immune evasion, and therapy resistance in cancer, yet these dynamic processes often escape detection by conventional sequencing and imaging approaches. Recent advances at the interface of nanotechnology, high-resolution live-cell imaging, and single-cell/spatial multiomics methods have enabled functional profiling of cells with unprecedented precision within their native microenvironment. In this Mini-Review, we highlight emerging nanoscale platforms that couple real-time phenotypic imaging with molecular readouts, such as FUNseq and CIN-seq, to directly link functional heterogeneity to transcriptomic, proteomic, and epigenomic information. By integrating nanoscale optical imaging, microengineered perturbation tools, and AI-driven computational analysis, these technologies open up new avenues for dissecting rare metastatic, therapy-resistant, or immune-evasive subpopulations. We further discuss how these next-generation imaging-guided single-cell and spatial omics platforms not only advance fundamental cancer biology but also create opportunities to accelerate the development of nanomedicine applications.

Humans↗
PubMed2026

Proteomics-based approaches to neutrophil biology.

INTRODUCTION: Neutrophils are central effectors of innate immunity and key contributors to inflammation, host defense, and tissue injury across a wide range of physiological and pathological contexts. Due to their short lifespan, rapid activation, and extensive post-translational regulation, comprehensive molecular characterization of neutrophil function requires approaches that go beyond transcriptomics or marker-based analyses. AREAS COVERED: This review summarizes how proteomic technologies have advanced the understanding of neutrophil biology by enabling unbiased, system-wide profiling of protein abundance, subcellular organization, post-translational modifications, and functional heterogeneity. We discuss global and subcellular proteomics, PTM-centric analyses, and emerging low-input and single-cell proteomic strategies, highlighting recent studies of infection, cancer, metabolic disorders, aging, autoimmune disease, and inflammation. The literature covered includes current large-scale quantitative proteomics, targeted PTMs, and integrative multi-omics studies in both human samples and relevant experimental models. EXPERT OPINION: Proteomics has established neutrophils as highly plastic and context-dependent cells whose functions are governed by coordinated remodeling of signaling, metabolism, and effector pathways. Future progress will depend on expanding neutrophil-specific PTM maps, improving low-input workflows, and integrating single-cell and spatial proteomics. Together, these advances are expected to redefine neutrophil functional states and accelerate translation toward clinically meaningful biomarkers and therapeutic strategies.

Humans↗
PubMed2006

Proteome chips for whole-organism assays.

Over the past 5 years, protein-chip technology has emerged as a useful tool for the study of many kinds of protein interactions and biochemical activities. The construction of Saccharomyces cerevisiae whole-proteome arrays has enabled further studies of such interactions in a proteome-wide context. Here, we explore some of the recent advances that have been made at the '-omic' level using protein microarrays.

Animals↗
PubMed2000

Proteome analysis of light-induced proteins in Synechocystis sp. PCC 6803: identification of proteins separated by 2D-PAGE using N-terminal sequencing and MALDI-TOF MS.

The cyanobacterium Synechocystis sp. PCC 6803 is an ideal model organism for the proteome study of light-induced gene expression because the whole genomic sequence has been determined. The soluble proteins extracted from light- and dark-cultured cells were separated by two-dimensional polyacrylamide gel electrophoresis. Light-induced protein spots electroblotted on a polyvinyldiene difluoride membrane were analyzed by N-terminal Edman sequence determination and followed by CyanoBase. The tryptic digests of some proteins were also confirmed by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) and MS-Fit search. Interestingly, eight proteins were related to photosynthesis and respiration (RbcS/L, CbbA, Gap2, AtpB, CpcB, PsbO, and PsbU). Four proteins (SodB, DnaK, GroEL2, and Tig) were involved in cellular processes and the functions of another two proteins (rehydrin and membrane protein) were unknown. The proteome analysis by N-terminal Edman sequencing and MALDI-TOF enabled us to characterize one-shot protein profiles expressed under different physiological conditions.

Amino Acid Sequence↗