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PubMed2025

Proteome organ aging and cardiometabolic risk in a population at risk for heart failure.

BACKGROUND: Biological aging varies across individuals and tissues, influencing chronic diseases, including heart failure (HF). Emerging proteome techniques enable quantification of organ-specific aging acceleration (OAA), but whether OAA relates to HF severity and differs by sex remains unclear. We aim to assess the sex-related association between OAA of heart, artery and kidneys and HF severity, and to investigate relevant cardiometabolic risk factors of organ aging. METHODS: In 556 participants from the HELPFul cohort, we estimated predicted biological age for heart, artery, and kidneys using plasma proteomics and calculated OAA as the deviation from chronological age. Associations between OAA and HF stage, echocardiographic parameters, and cardiometabolic risk factors were evaluated using regression models. Composite indices, including triglyceride-glucose body mass index (TyG-BMI), c-reactive protein-triglyceride glucose index and triglyceride-to-HDL cholesterol ratio were assessed for associations with advanced OAA. RESULTS: Mean age was 63 ± 9 years; 65% were women. Patients were classified as HF stage A (35%), B (29%) and C/D (36%). Heart OAA was significantly associated with advanced HF (Stage C/D) in both sexes (OR = 1.12, 95% CI 1.03 to 1.23 in women; OR = 1.18, 95% CI 1.05 to 1.32 in men), while artery OAA was linked to HF only in women (OR = 1.10, 95% CI 1.01 to 1.18). Multi-organ aging (≥ 2 organs with advanced OAA) conferred over three-fold higher odds of being in Stage C/D. Heart OAA correlated with impaired cardiac structure and function, particularly reduced ejection fraction in men and increased left ventricular mass index in both sexes. Diabetes emerged as the most relevant factor of artery and kidney OAA. TyG-BMI was significantly associated with advanced kidney OAA, only in women (z-scored OR = 1.88, 95% CI 1.45 to 2.45). CONCLUSIONS: Proteome-derived organ aging correlates with HF severity, with possible sex-related patterns. Diabetes and higher TyG-BMI are associated with faster organ aging, which may reflect shared aging mechanisms between metabolic dysfunction and HF.

Humans↗

PubMed2005

The microsporidian polar tube: a highly specialised invasion organelle.

All of the members of the Microsporidia possess a unique, highly specialised structure, the polar tube. This article reviews the available data on the organisation, structure and function of this invasion organelle. It was over 100 years ago that Thelohan accurately described the microsporidian polar tube and the triggering of its discharge. In the spore, the polar tube is connected at the anterior end, and then coils around the sporoplasm. Upon appropriate environmental stimulation the polar tube rapidly discharges out of the spore pierces a cell membrane and serves as a conduit for sporoplasm passage into the new host cell. The mechanism of germination of spores, however, remains to be definitively determined. In addition, further studies on the characterisation of the early events in the rupture of the anterior attachment complex, eversion of the polar tube as well as the mechanism of host cell attachment and penetration are needed in order to clarify the function and assembly of this structure. The application of immunological and molecular techniques has resulted in the identification of three polar tube proteins referred to as PTP1, PTP2 and PTP3. The interactions of these identified proteins in the formation and function of the polar tube remain to be determined. Data suggest that PTP1 is an O-mannosylated glycoprotein, a post-translational modification that may be important for its function. With the availability of the Encephalitozoon cuniculi genome it is now possible to apply proteomic techniques to the characterisation of the components of the microsporidian spore and invasion organelle.

Fungal Proteins↗

PubMed2005

From proteomics to biomarker discovery in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD is an invariably fatal neurodegenerative disorder with no effective treatment or definitive antemortem diagnostic test. Little is known about the changes in the brain preceding or accompanying initiation of the disease. Understanding the biological processes, which occur during AD onset and/or progression, will improve the diagnosis and treatment of the disease. As we will discuss in this review article, using high-throughput cDNA microarray we identified candidate genes whose expression is altered in the brain of cases at risk for AD dementia. However, it is possible that the use of the cDNA microarray technology alone may underestimate post-transcriptional modifications and therefore provides only a partial view of the biological problem of interest. As such, the combination of cDNA and protein arrays may provide a more global picture of the biological processes being studied. Based on this hypothesis, we initiated a series of high-throughput proteomic studies and found that the expressions of proteins involved in synaptic plasticity are selectively altered in the brain of cases at high risk to develop AD dementia (mild cognitive impairment; MCI). This is consistent with our cDNA microarray evidence showing that the expression of a-type synapsins is selectively altered in the brain of MCI cases. Collectively, these studies support the feasibility and usefulness of high-throughput cDNA microarray and proteomics techniques to study the sequential changes of distinctive gene expression patterns in the brain as a function of the progression of AD dementia.

Alzheimer Disease↗

PubMed2007

A proteomic analysis of adult rat bone reveals the presence of cartilage/chondrocyte markers.

The non-mineral component of bone matrix consists of 90% collagenous, 10% non-collagenous proteins. These proteins regulate mineralization, growth, cell signaling and differentiation, and provide bone with its tensile strength. Expression of bone matrix proteins have historically been studied individually or in small numbers owing to limitations in analytical technologies. Current mass-spectrometric and separations technologies allow a global view of protein expression patterns in complex samples. To our knowledge, no proteome profile of bone matrix has yet been reported. Therefore, we have used mass spectrometry as a tool to generate a profile of proteins present in the extracellular matrix of adult rat bone. Overall, 108 and 25 proteins were identified with high confidence in the metaphysis and diaphysis, respectively, using a bottom up proteomic technique. Twenty-one of these proteins were present in both the metaphysis and diaphysis including the bone specific proteins, osteocalcin, type I collagen, osteopontin, osteoregulin, and bone sialoprotein. Interestingly, type II collagen, a protein thought to be exclusively expressed in cartilage, was identified in both the metaphysis and diaphysis. This observation was validated by Western blot. Additionally, the presence of aggrecan, another protein expressed in cartilage was identified in the bone matrix extracts by Western blot. The proteome profile generated using this technology represents an initial survey of the acid soluble proteins of bone matrix which provides a reference for the analysis of deviations from the normal composition due to perturbations or disease states.

Aggrecans↗

PubMedDate not supplied

Uncovering the unfoldome: enriching cell extracts for unstructured proteins by acid treatment.

A method to enrich cell extracts in totally unfolded proteins was investigated. A literature search revealed that 14 of 29 proteins isolated by their failure to precipitate during perchloric acid (PCA) or trichloroacetic acid (TCA) treatment where also shown experimentally to be totally disordered. A near 100 000-fold reduction in yield was observed after 5% or 9% PCA treatment of total soluble E. coli protein. Despite this huge reduction, 158 and 142 spots were observed from the 5% and the 9% treated samples, respectively, on silver-stained 2-D SDS-PAGE gels loaded with 10 microg of protein. Treatment with 1% PCA was less selective with more visible spots and a greater than 3-fold higher yield. A substantial yield of unprecipitated protein was obtained after 3% TCA treatment, suggesting that the common use of TCA precipitation prior to 2-D gel analysis may result in loss of unstructured protein due to their failure to precipitate. Our preliminary analysis suggests that treating total protein extracts with 3-5% PCA and determining the identities of soluble proteins could be the starting point for uncovering unfoldomes (the complement of unstructured proteins in a given proteome). The 100 000-fold reduction in yield and concomitant reduction in number of proteins achieved by 5% PCA treatment produced a fraction suitable for analysis in its entirety using standard proteomic techniques. In this way, large numbers of totally unstructured proteins could be identified with minimal effort.

Bacterial Proteins↗

PubMed2005

Biomarkers: mining the biofluid proteome.

Proteomics has brought with it the hope of identifying novel biomarkers for diseases such as cancer. This hope is built on the ability of proteomic technologies, such as mass spectrometry (MS), to identify hundreds of proteins in complex biofluids such as plasma and serum. There are many factors that make this research very challenging beginning with the lack of standardization of sample collection and continuing through the entire analytical process. Fortunately the advances made in the characterization of biofluids using proteomic techniques have been rapid and suggest that these mainly discovery driven approaches will lead to the development of highly specific platforms for diagnosing diseases and monitoring responses to different treatments in the near future.

Biomarkers↗

PubMed2005

Understanding protein trafficking in plant cells through proteomics.

The functions of approximately one-third of the proteins encoded by the Arabidopsis thaliana genome are completely unknown. Moreover, many annotations of the remainder of the genome supply tentative functions, at best. Knowing the ultimate localization of these proteins, as well as the pathways used for getting there, may provide clues as to their functions. The putative localization of most proteins currently relies on in silico-based bioinformatics approaches, which, unfortunately, often result in erroneous predictions. Emerging proteomics techniques coupled with other systems biology approaches now provide researchers with a plethora of methods for elucidating the final location of these proteins on a large scale, as well as the ability to dissect protein-sorting pathways in plants.

Databases, Protein↗

PubMed2006

Towards exposure of elusive metabolic mixed-culture processes: the application of metaproteomic analyses to activated sludge.

Protein expression is a direct reflection of specific microbial activities in any ecosystem. In order to assess protein expression in mixed microbial communities, the feasibility of applying proteomic techniques to activated sludge samples has recently been demonstrated. We report the application of metaproteomics to two activated sludges from a laboratory-scale sequencing batch reactor with dissimilar phosphorus removal performances. Fluorescence in situ hybridization (FISH) revealed that the sludge with good enhanced biological phosphorus removal performance (EBPR) was dominated by Betaproteobacteria (65% of EUBMIX binding cells) and gave positive signals for the Rhodocyclus-type PAO specific probe (59%). The non-EBPR sludge was dominated by tetrad-forming Alphaproteobacteria (75%). With regard to the proteomic investigation, 630 individual protein spots were matched across the replicate groups of the anaerobic and aerobic phases of the EBPR sludge with 9.4% of all spots being statistically different between the two phases. The non-EBPR metaproteomic maps exhibited 590 matched spots with 14.7% statistical differences between the two phases. Overall, the non-EBPR sludge expressed around 30% more significant differences than the EBPR sludge. The comparison of protein expression in the two sludges showed that their metaproteomes were substantially different and this was reflected in their microbial community structures and metabolic transformations.

Base Sequence↗

PubMed2006

Proteomic analysis of fast and slow muscles from normal and kyphoscoliotic mice using protein arrays, 2-DE and MS.

A proteomic strategy based upon the integrated use of SELDI-TOF/MS, 2-DE and MALDI-TOF/MS has been used to identify a panel of fast muscle protein markers: MLC1F, MLC3F, fast troponin C (STNC) and slow muscle markers: MLC1SB and MLC2v. MLC3F, MLC1F and STNC were virtually absent in the physiologically pure slow soleus muscle of kyphoscoliotic mutant mice compared to control BDmice, whereas MLC2v increased threefold. A SELDI-TOF/MS peak at 18,012 Da in spectra from strong anionic exchange protein array fractions of fast vastus muscle was confirmed as STNC by its specific depletion from crude extracts of vastus muscle using an anti-TNC mAb. SELDI-TOF/MS also identified MLC2F phosphorylation in crude muscle extracts after treatment with alkaline phosphatase. High probability protein identifications were achieved by SELDI-TOF/MS PMF based upon the resolution of large peptides formed by partial cleavage and high peptide coverage. When the pI from 2-D gels and molecular weight estimations from SELDI-TOF/MS were entered into the TagIdent algorithm, high probability protein identity predictions were obtained that were confirmed later by PMF. We confirm that SELDI-TOF/MS can be integrated with other proteomics techniques for the efficient analysis of protein expression changes and PTMs associated with physiological changes in skeletal muscle.

Animals↗

PubMedDate not supplied

Differential display proteome analysis of PC-12 cells transiently transfected with metallothionein-3 gene.

Metallothionein-3 (MT-3), also known as growth inhibitory factor, possesses several unique properties other than the common features of metallothionein family. To investigate the mechanisms underlying its multifaceted roles in the central nervous system, we employed differential display proteomics techniques to study holistic protein changes of PC-12 cells induced by transient transfection of MT-3. Ten significantly and reproducibly changed proteins were identified and their functional implications are discussed in some detail.

Animals↗

PubMed2005

Differential proteomic serum pattern of low molecular weight proteins expressed by adenocarcinoma lung cancer patients.

Based on the assumption that proteins can emanate from tumour to serum, we investigated whether serum low molecular weight proteins (LMW) can discriminate lung cancer patients from healthy donors. Pooled sera from 20 lung cancer patients matched in sex (men), histological type (adenocarcinoma) and stage (IIIB and IV) and from 20 healthy donors (men) were submitted to 2-DE coupled to MALDI-TOF peptide mass fingerprinting. Results of 2D-E/ MALDI-TOF showed five up regulated proteins (immunoglobulin lambda chain, transthyretin monomer, haptoglobin-alfa 2 and two isoforms of serum amyloid protein) and one down regulated (fragment of apolipoprotein A-I) in patients. All differentially expressed proteins, except immunoglobulin, may be acting as a non-specific sign of inflammation in cancer and transthyretin monomer may act as a possible blood marker to CSF barrier disruption that occurs, e.g., in cerebral metastasis. In conclusion, this work shows the usefulness of 2D-gel electrophoresis and mass spectrometry proteomic techniques for the identification of up- and down-regulated proteins in serum from adenocarcinoma lung cancer patients.

Adenocarcinoma↗

PubMedDate not supplied

Proteome analysis of antiproliferative mechanism of 12-O-tetradecanoylphorbol 13-acetate on cultured nasopharyngeal carcinoma CNE2 cells.

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) is a plant derivative with multiple function as tumor promoter, differentiation revulsant or leukemia therapy drug. The molecular mechanism of its function is perplexing. Many studies have focused on the mechanism of TPA stimulation in tumor promotion of mouse models or terminal differentiation of leukemia cells, but the effect of TPA on nasopharyngeal carcinoma (NPC) remains unclear, while TPA was considered to be associated with NPC development. In the present study, we employed proteomics techniques to study protein changes of a poorly differentiated squamous carcinoma cell line-CNE2 of human NPCs cells induced by TPA. Six significantly and reproducibly changed proteins were identified and their functional implications were discussed in some details.

Base Sequence↗

PubMed2004

Large scale gene expression profiling of metabolic shift of mammalian cells in culture.

The metabolic state of hybridoma cells in continuous culture varies with the cultivation condition from which the culture is initiated. At a metabolically shifted state, cells have markedly reduced glucose and other nutrient consumption and lactate production as compared to cells in batch culture or in continuous culture without a metabolic shift. Taking a combined genomics and proteomics approach, we investigated the molecular mechanism of metabolic shift. Cells from continuous cultures at two different steady states with a glucose consumption to lactate production molar ratio (DeltaL/DeltaG) of 0.08 and 1.4 were studied. Affymetrix GeneChips as well as cDNA microarrays were employed to identify differentially expressed mRNA transcripts, and the differentially expressed proteins were identified using the 2D gel electrophoresis-mass spectrometry approach. The decrease in glucose metabolism upon metabolic shift is accompanied by a decrease in gene expression of a number of genes involved in its metabolism. However, the number of genes differentially expressed and the extent of differential expression upon metabolic shift are relatively moderate. The change in the expression of metabolic genes at the transcriptional level was confirmed by real time PCR. The results suggest that metabolic shift is a combined effect of both biochemical events at reaction level and gene expression at transcription and translation level. This approach of integrating transcriptional profiling, proteomic techniques and biochemical analysis provides a more global view of the metabolism of mammalian cells in culture.

Animals↗

PubMed2006

[Proteomic analysis of paclitaxel-induced apoptosis in MCF-7 human breast carcinoma cells].

OBJECTIVE: To investigate the mechanism of paclitaxel-induced apoptosis in MCF-7 human breast carcinoma cells. METHODS: In this study, the proteins extracted from paclitaxel-induced apoptotic MCF-7 cells were analyzed by 2-dimentional gel electrophoresis (2-DE), and compared with those from untreated MCF-7 cells. The differential proteins were identified by mass spectrometry. RESULTS: At 24 hour after paclitaxel (100 nmol/L) treatment, MCF-7 cells were collected and extracted the whole proteins. Seventeen up-regulated or down-regulated proteins were found by analysis of the differential proteomic 2-DE map. Six of them were identified by mass spectrometry. They were enolase 1, chloride intracellular channel 1, keratin 8, ribosomal protein S12, galectin-1 and histidine triad nucleotide binding protein, respectively. CONCLUSION: We effectively found the changed proteins in the process of paclitaxel-induced apoptosis in MCF-7 human breast carcinoma cells by proteomic techniques. These up-regulated or down-regulated proteins are important molecules for our further research about the mechanism of paclitaxel-induced apoptosis.

Antineoplastic Agents, Phytogenic↗

PubMed2026

AI-driven diagnostic and prognostic models for metabolic dysfunction-associated steatotic liver disease: insights from clinical, imaging, and multi-omics studies-a scoping review.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease around the world, affecting 33.6% of the adult population (95% CI: 28.1%-39.5%; I 2 = 99.9%), or roughly one in three. The extent of the liver damage is variable, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), cirrhosis and hepatocellular carcinoma (HCC). Early diagnosis is essential to prevent serious liver damage. Traditional diagnostic techniques such as liver biopsy, imaging, and biomarker testing are all invasive, costly, reduced sensitive to early-stage disease, and they also have variability among observers. Modern diagnostic and prognostic approaches based on the principles of Artificial Intelligence (AI) and specifically on machine learning (ML) and deep learning (DL) have enabled multimodal approaches integrating clinical, imaging and molecular data. This scoping review conducted per PRISMA-ScR guidelines, synthesizes findings from 73 studies (search window 2020-2026) across three dimensions: clinical data driven models, imaging-based classifiers (ultrasound, CT and MRI), and multi-omics (genomics, transcriptomics and proteomics) techniques. Moreover, emergence of models such as U-Net and LiverNet 2.x, classification models like DeepLiverNet and BiLSTM models, as well as transformer frameworks and the identification of biomarkers models are also described. This study also investigates challenges such as data heterogeneity, data interpretability, fairness and real-world clinical application. Finally, important areas of research opportunities and future directions are highlighted to present a developing clinically applicable, explainable and ethical AI solutions to manage MASLD.

MASLD↗

PubMed2004

Expression, by functional proteomics, of spontaneous tolerance in rat orthotopic liver transplantation.

Orthotopic liver transplants (OLT) performed in certain combinations of donor and recipient rat strains, such as DA (RT1a) to PVG (RT1c), without immunosuppressive drugs could completely overcome major histocompatibility complex barriers. Although other organs transplanted in a similar fashion within the same combination have been promptly rejected, 60 day post-OLT serum (POD 60) has been proven competent in rapidly reversing the established rejection in animal models. In order to understand the functional role of tolerogenic serum proteins and their involvement with immune response regulation, a comprehensive analysis surveying global changes in complex OLT systems by proteomic techniques was applied. The results display the varying protein expressions in sera extracted from naïve and transplanted animals on POD 60 with regard to immunosuppression. Among these proteins, haptoglobin (Hp) which is related to inhibition of T-cell proliferation was found to be up-regulated following OLT. In addition, the transcriptional expression level and intracellular localization of Hp correlated with the immune events. Hp also exhibited a strong in vitro immunosuppressive effect on the mixed lymphocyte reaction. In conclusion, the presence of Hp may play an important role in modulating the spontaneous tolerance of liver transplantation. Furthermore, the serum proteome map could provide guidance with respect to discovering potential protein targets in OLT tolerance and eventually prolong hepatic allograft survival in the future.

Amino Acid Sequence↗

PubMed2006

Phospho-proteomic analysis of cellular signaling.

Reversible protein phosphorylation plays an important role in the regulation of many different processes, such as cell growth, differentiation, migration, metabolism, and apoptosis. Identification of differentially phosphorylated proteins by means of phospho-proteomic analysis provides insight into signal transduction pathways that are activated in response to, for example, growth factor stimulation or toxicant-induced apoptosis. This review summarizes recent advances made in the field of phospho-proteomics and provides examples of how phospho-proteomic techniques can be combined to quantitatively investigate the dynamic changes in protein phosphorylation in time. By linking experimental data to clinical data (e.g., disease progression or response to therapy) new disease markers could be identified, which could then be validated for applications in disease diagnosis and progression or prediction of a response to drugs.

Animals↗

PubMed2006

Neuroproteomics - the tasks lying ahead.

The brain is unquestionably the most fascinating organ. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward improved understanding of the molecular mechanisms underlying brain function is neuroproteomics. Today's neuroscientists have access to a battery of versatile technologies both in transcriptomics and proteomics. The challenge is to choose the right strategy in order to generate new hypotheses on how the brain works. The goal of this review is therefore two-fold: first we recall the bewildering cellular, molecular, and functional complexity in the brain, as this knowledge is fundamental to any study design. In fact, an impressive complexity on the molecular level has recently re-emerged as a central theme in large-scale analyses. Then we review transcriptomics and proteomics technologies, as both are complementary. Finally, we comment on the most widely used proteomics techniques and their respective strengths and drawbacks. We conclude that for the time being, neuroproteomics should focus on its strengths, namely the identification of posttranslational modifications and protein-protein interactions, as well as the characterization of highly purified subproteomes. For global expression profiling, emphasis should be put on further development to significantly increase coverage.

Brain↗