Proteomes最新文献

{"title":"Intrinsic Disorder and Phase Separation Coordinate Exocytosis, Motility, and Chromatin Remodeling in the Human Acrosomal Proteome.","authors":"Shivam Shukla, Sean S Lastorka, Vladimir N Uversky","doi":"10.3390/proteomes13020016","DOIUrl":"10.3390/proteomes13020016","url":null,"abstract":"<p><p>Intrinsic disorder refers to protein regions that lack a fixed three-dimensional structure under physiological conditions, enabling conformational plasticity. This flexibility allows for diverse functions, including transient interactions, signaling, and phase separation via disorder-to-order transitions upon binding. Our study focused on investigating the role of intrinsic disorder and liquid-liquid phase separation (LLPS) in the human acrosome, a sperm-specific organelle essential for fertilization. Using computational prediction models, network analysis, Structural Classification of Proteins (SCOP) functional assessments, and Gene Ontology, we analyzed 250 proteins within the acrosomal proteome. Our bioinformatic analysis yielded 97 proteins with high levels (>30%) of structural disorder. Further analysis of functional enrichment identified associations between disordered regions overlapping with SCOP domains and critical acrosomal processes, including vesicle trafficking, membrane fusion, and enzymatic activation. Examples of disordered SCOP domains include the PLC-like phosphodiesterase domain, the t-SNARE domain, and the P-domain of calnexin/calreticulin. Protein-protein interaction networks revealed acrosomal proteins as hubs in tightly interconnected systems, emphasizing their functional importance. LLPS propensity modeling determined that over 30% of these proteins are high-probability LLPS drivers (>60%), underscoring their role in dynamic compartmentalization. Proteins such as myristoylated alanine-rich C-kinase substrate and nuclear transition protein 2 exhibited both high LLPS propensities and high levels of structural disorder. A significant relationship (<i>p</i> < 0.0001, R² = 0.649) was observed between the level of intrinsic disorder and LLPS propensity, showing the role of disorder in facilitating phase separation. Overall, these findings provide insights into how intrinsic disorder and LLPS contribute to the structural adaptability and functional precision required for fertilization, with implications for understanding disorders associated with the human acrosome reaction.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Extracellular Vesicle (sEV) Uptake from Lung Adenocarcinoma and Squamous Cell Carcinoma Alters T-Cell Cytokine Expression and Modulates Protein Profiles in sEV Biogenesis.","authors":"Hafiza Padinharayil, Jinsu Varghese, Pulikkottil Raphael Varghese, Cornelia M Wilson, Alex George","doi":"10.3390/proteomes13020015","DOIUrl":"10.3390/proteomes13020015","url":null,"abstract":"<p><strong>Background: </strong>Despite advances in immunotherapy, non-small-cell lung carcinoma (NSCLC)'s clinical success is limited, possibly due to substantial immunological alterations in advanced cancer patients. This study examines the immunomodulatory effects of sEVs derived from lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on T cells.</p><p><strong>Methods: </strong>SEVs were isolated from lung cancer cell lines and Jurkat-E6.1. SEV size and morphology were analyzed by NTA and TEM, respectively, while Western blotting confirmed sEV markers. SEV uptake was assessed, followed by resazurin assay, RNA isolation, quantification, cDNA preparation, RT-PCR, nano LC-MS, and bioinformatic analysis, before and after treating Jurkat-E6.1 cells with sEVs from A549 and SKMES1.</p><p><strong>Results: </strong>Cancer-derived sEVs were efficiently internalized by immune cells, reducing T-cell viability. The real-time PCR analysis showed downregulation of KI67, BCL2, BAX, TNFA, IL6, TGFβ, and IL10, suggesting reduced proliferation, dysregulated apoptosis, and impaired inflammatory and immunosuppressive signaling, and the upregulation of GZMB and IL2 suggests retained cytotoxic potential but possibly dysfunctional T-cell activation. Proteomic analysis revealed 39 differentially abundant proteins (DAPs) in ADC-treated T cells and 276 in SCC-treated T cells, with 19 shared DAPs. Gene Ontology (GO) analysis of these DAPs highlighted processes such as sEV biogenesis, metabolic pathways, and regulatory functions, with ADC sEVs influencing NAD metabolism, ECM binding, and oxidoreductase activity, while SCC sEVs affected mRNA stability, amino acid metabolism, and cadherin binding. The cytoplasmic colocalization suggests the presence of these proteins in the cellular and extracellular lumen, indicating the potential of further release of these proteins in the vesicles by T cells.</p><p><strong>Conclusion: </strong>Lung cancer-derived sEVs regulate T-cell activities through immunoregulatory signaling. The molecular interactions between sEVs and immune cells can reveal novel tumor immune regulatory mechanisms and therapeutic targets.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of LIN28B in the Regulation of Ribosomal Biogenesis and Lipid Metabolism in Medulloblastoma Brain Cancer Cells.","authors":"Ahmed Maklad, Mohammed Sedeeq, Kaveh Baghaei, Richard Wilson, John A Heath, Nuri Gueven, Iman Azimi","doi":"10.3390/proteomes13020014","DOIUrl":"https://doi.org/10.3390/proteomes13020014","url":null,"abstract":"<p><p><b>Background:</b> Medulloblastoma (MB) is the most aggressive paediatric brain cancer, highlighting the urgent need for new diagnostic and prognostic biomarkers and improved treatments to enhance patient outcomes. Our previous study identified LIN28B, an RNA-binding protein, as a potential diagnostic and prognostic marker for MB and a pharmacological target to inhibit MB cell proliferation and stemness. However, the specific role of LIN28B and its mechanism of action in MB had not been studied. <b>Methods:</b> This study assessed LIN28B's role in Daoy MB cells using siRNA-mediated silencing. LIN28B silencing was achieved with Dharmacon ON-TARGETplus SMARTpool and confirmed by Western blotting. Proliferation and protein assays evaluated the cell metabolic activity and viability. A proteomics analysis was conducted to examine the effect of LIN28B knockdown on the MB cell protein expression profile. The intracellular lipid droplets were assessed using the Nile Red Staining Kit, and nucleolar B23 protein levels were assessed by immunofluorescence. Both were visualised with a high-content IN Cell Analyser 2200. <b>Results:</b> Effective LIN28B silencing (>80%) was achieved in each experiment. LIN28B knockdown reduced the MB cell viability, impaired ribosome biogenesis, and promoted cellular lipid accumulation, as supported by proteomics and cell-based assays. <b>Conclusions:</b> This study highlights LIN28B as a promising target for regulating MB cell growth, ribosomal biogenesis, and lipid metabolism.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Type-Specific Heat-Induced Changes in the Proteomes of Pollen Mother Cells and Microspores Provide New Insights into Tomato Pollen Production Under Elevated Temperature.","authors":"Priya Thapa, Jun Guo, Kajol Pradhan, Dibya Thapa, Sudhakar Madhavarapu, Jing Zou, Jesse Potts, Hui Li, Joshua O'Hair, Chen Wang, Suping Zhou, Yong Yang, Tara Fish, Theodore W Thannhauser","doi":"10.3390/proteomes13020013","DOIUrl":"https://doi.org/10.3390/proteomes13020013","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Tomatoes are self-pollinating plants, and successful fruit set depends on the production of functional pollen within the same flower. Our previous studies have shown that the 'Black Vernissage' tomato variety exhibits greater resilience to heat stress in terms of pollen productivity compared to the 'Micro-Tom' variety. Pollen productivity is determined by meiotic activity during microsporogenesis and the development of free microspores during gametogenesis. This study focused on identifying heat stress (HS)-induced proteomes in pollen mother cells (PMCs) and microspores.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Tomato plants were grown under two temperature conditions: 26 °C (non-heat-treated control) and 37 °C (heat-treated). Homogeneous cell samples of meiotic PMCs (prior to the tetrad stage) and free microspores were collected using laser capture microdissection (LCM). The heat-induced proteomes were identified using tandem mass tag (TMT)-quantitative proteomics analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The enrichment of the meiotic cell cycle in PMCs and the pre-mitotic process in free microspores confirmed the correlation between proteome expression and developmental stage. Under HS, PMCs in both tomato varieties were enriched with heat shock proteins (HSPs). However, the 'Black Vernissage' variety exhibited a greater diversity of HSP species and a higher level of enrichment compared to the 'Micro-Tom' variety. Additionally, several proteins involved in gene expression and protein translation were downregulated in PMCs and microspores of both varieties. In the PMC proteomes, the relative abundance of proteins showed no significant differences between the two varieties under normal conditions, with very few exceptions. However, HS induced significant differential expression both within and between the varieties. More importantly, these heat-induced differentially abundant proteins (DAPs) in PMCs are directly involved in meiotic cell division, including the meiosis-specific protein ASY3 (Solyc01g079080), the cell division protein kinase 2 (Solyc11g070140), COP9 signalosome complex subunit 1 (Solyc01g091650), the kinetochore protein ndc80 (Solyc01g104570), MORC family CW-type zinc finger 3 (Solyc02g084700), and several HSPs that function in protecting the fidelity of the meiotic processes, including the DNAJ chaperone (Solyc04g009770, Solyc05g055160), chaperone protein htpG (Solyc04g081570), and class I and class II HSPs. In the microspores, most of the HS-induced DAPs were consistently observed across both varieties, with only a few proteins showing significant differences between them under heat stress. These HS-induced DAPs include proteases, antioxidant proteins, and proteins related to cell wall remodeling and the generation of pollen exine.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;HS induced more dynamic proteomic changes in meiotic PMCs compared to microspores, and the inter-varietal differences in the PMC proteomes ali","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics of Extracellular Vesicles: Recent Updates, Challenges and Limitations.","authors":"Mohini Singh, Prashant Kumar Tiwari, Vivek Kashyap, Sanjay Kumar","doi":"10.3390/proteomes13010012","DOIUrl":"10.3390/proteomes13010012","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are lipid-bound vesicles secreted by cells, including exosomes, microvesicles, and apoptotic bodies. Proteomic analyses of EVs, particularly in relation to cancer, reveal specific biomarkers crucial for diagnosis and therapy. However, isolation techniques such as ultracentrifugation, size-exclusion chromatography, and ultrafiltration face challenges regarding purity, contamination, and yield. Contamination from other proteins complicates downstream processing, leading to difficulties in identifying biomarkers and interpreting results. Future research will focus on refining EV characterization for diagnostic and therapeutic applications, improving proteomics tools for greater accuracy, and exploring the use of EVs in drug delivery and regenerative medicine. In this review, we provide a bird's eye view of various challenges, starting with EV isolation methods, yield, purity, and limitations in the proteome analysis of EVs for identifying protein targets.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Comparison of Acute Myeloid Leukemia Cells and Normal CD34⁺ Bone Marrow Cells: Studies of Leukemia Cell Differentiation and Regulation of Iron Metabolism/Ferroptosis.","authors":"Frode Selheim, Elise Aasebø, Håkon Reikvam, Øystein Bruserud, Maria Hernandez-Valladares","doi":"10.3390/proteomes13010011","DOIUrl":"10.3390/proteomes13010011","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy that can be cured only by intensive chemotherapy possibly combined with allogeneic stem cell transplantation. We compared the pretreatment proteomic profiles of AML cells derived from 50 patients at the time of first diagnosis with normal CD34⁺ bone marrow cells. A comparison based on all AML and CD34⁺ normal cell populations identified 121 differentially abundant proteins that showed at least 2-fold differences, and these proteins included several markers of neutrophil differentiation (e.g., TLR2, the integrins ITGM and ITGX, and downstream mediators including RHO GTPase, S100A8, S100A9, S100A22). However, the expression of these 121 proteins varied between patients, and a subset of 28 patients was characterized by increased long-term AML-free survival, signs of myeloid AML cell differentiation, and favorable genetic abnormalities. These two main patient subsets (28 with differentiation versus 22 with fewer signs of differentiation) also differed with regard to the phosphorylation of 16 differentially abundant proteins. Furthermore, we also classified our patients based on their expression of 16 proteins involved in the regulation of iron metabolism/ferroptosis and showing differential expression when comparing AML cells and normal CD34+ cells. Among the 22 patients with less favorable prognosis, we could then identify a genetically heterogeneous subset characterized by adverse prognosis (i.e., death from primary resistance/relapse) and an iron metabolism/ferroptosis protein profile showing similarities with normal CD34⁺ cells. We conclude that proteomic profiles differ between AML and normal CD34⁺ cells; especially, proteomic differences reflecting differentiation and regulation of iron metabolism/ferroptosis are associated with risk of relapse after intensive conventional therapy.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-Based Deep Learning Framework for Modeling Human-Gut Bacterial Protein Interactions.","authors":"Despoina P Kiouri, Georgios C Batsis, Christos T Chasapis","doi":"10.3390/proteomes13010010","DOIUrl":"10.3390/proteomes13010010","url":null,"abstract":"<p><p><b>Background:</b> The interaction network between the human host proteins and the proteins of the gut bacteria is essential for the establishment of human health, and its dysregulation directly contributes to disease development. Despite its great importance, experimental data on protein-protein interactions (PPIs) between these species are sparse due to experimental limitations. <b>Methods:</b> This study presents a deep learning-based framework for predicting PPIs between human and gut bacterial proteins using structural data. The framework leverages graph-based protein representations and variational autoencoders (VAEs) to extract structural embeddings from protein graphs, which are then fused through a Bi-directional Cross-Attention module to predict interactions. The model addresses common challenges in PPI datasets, such as class imbalance, using focal loss to emphasize harder-to-classify samples. <b>Results:</b> The results demonstrated that this framework exhibits robust performance, with high precision and recall across validation and test datasets, underscoring its generalizability. By incorporating proteoforms in the analysis, the model accounts for the structural complexity within proteomes, making predictions biologically relevant. <b>Conclusions:</b> These findings offer a scalable tool for investigating the interactions between the host and the gut microbiota, potentially yielding new treatment targets and diagnostics for disorders linked to the microbiome.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems Biology of Recombinant 2G12 and 353/11 mAb Production in CHO-K1 Cell Lines at Phosphoproteome Level.","authors":"Eldi Sulaj, Felix L Sandell, Linda Schwaigerlehner, Gorji Marzban, Juliane C Dohm, Renate Kunert","doi":"10.3390/proteomes13010009","DOIUrl":"10.3390/proteomes13010009","url":null,"abstract":"<p><p><b>Background</b>: Chinese hamster ovary (CHO) cells are extensively used in the pharmaceutical industry for producing complex proteins, primarily because of their ability to perform human-like post-translational modifications. However, the efficiency of high-quality protein production can vary significantly for monoclonal antibody-producing cell lines, within the CHO host cell lines or by extrinsic factors. <b>Methods</b>: To investigate the complex cellular mechanisms underlying this variability, a phosphoproteomics analysis was performed using label-free quantitative liquid chromatography after a phosphopeptide enrichment of recombinant CHO cells producing two different antibodies and a tunicamycin treatment experiment. Using MaxQuant and Perseus for data analysis, we identified 2109 proteins and quantified 4059 phosphosites. <b>Results</b>: Significant phosphorylation dynamics were observed in nuclear proteins of cells producing the difficult-to-produce 2G12 mAb. It suggests that the expression of 2G12 regulates nuclear pathways based on increases and decreases in phosphorylation abundance. Furthermore, a substantial number of changes in the phosphorylation pattern related to tunicamycin treatment have been detected. TM treatment affects, among other phosphoproteins, the eukaryotic elongation factor 2 kinase (Eef2k). <b>Conclusions</b>: The alterations in the phosphorylation landscape of key proteins involved in cellular processes highlight the mechanisms behind stress-induced cellular responses.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Endogenous Proteins of Perennial Ryegrass (<i>Lolium perenne</i>) with <i>Ex Vivo</i> Antioxidant Activity.","authors":"Kathrine Danner Aakjær Pedersen, Line Thopholm Andersen, Mads Heiselberg, Camilla Agerskov Brigsted, Freja Lyngs Støvring, Louise Mailund Mikkelsen, Sofie Albrekt Hansen, Christian Enrico Rusbjerg-Weberskov, Mette Lübeck, Simon Gregersen Echers","doi":"10.3390/proteomes13010008","DOIUrl":"10.3390/proteomes13010008","url":null,"abstract":"<p><p><b>Background</b>: During the initial steps of green biorefining aimed at protein recovery, endogenous proteins and enzymes, along with, e.g., phytochemical constituents, are decompartmentalized into a green juice. This creates a highly dynamic environment prone to a plethora of reactions including oxidative protein modification and deterioration. Obtaining a fundamental understanding of the enzymes capable of exerting antioxidant activity <i>ex vivo</i> could help mitigate these reactions for improved product quality. <b>Methods</b>: In this study, we investigated perennial ryegrass (<i>Lolium perenne</i> var. Abosan 1), one of the most widely used turf and forage grasses, as a model system. Using size exclusion chromatography, we fractionated the green juice to investigate <i>in vitro</i> antioxidant properties and coupled this with quantitative bottom-up proteomics, GO-term analysis, and fraction-based enrichment. <b>Results</b>: Our findings revealed that several enzymes, such as superoxide dismutase and peroxiredoxin proteoforms, already known for their involvement in <i>in vivo</i> oxidative protection, are enriched in fractions displaying increased <i>in vitro</i> antioxidant activity, indicating retained activity <i>ex vivo</i>. Moreover, this study provides the most detailed characterization of the <i>L. perenne</i> proteome today and delivers new insights into protein-level partitioning during wet fractionation. <b>Conclusions</b>: Ultimately, this work contributes to a better understanding of the first steps of green biorefining and provides the basis for process optimization.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Signaling Pathways Identified in Aqueous Humor, Anterior Capsule, and Crystalline Lens of Age-Related, Diabetic, and Post-Vitrectomy Cataract.","authors":"Christina Karakosta, Martina Samiotaki, Anastasios Bisoukis, Konstantinos I Bougioukas, George Panayotou, Dimitrios Papaconstantinou, Marilita M Moschos","doi":"10.3390/proteomes13010007","DOIUrl":"10.3390/proteomes13010007","url":null,"abstract":"<p><p><b>Background</b>: The purpose of this study was to detect proteomic alterations and corresponding signaling pathways involved in the formation of age-related cataract (ARC), diabetic cataract (DC), and post-vitrectomy cataract (PVC). <b>Methods</b>: Three sample types, the aqueous humor (AH), the anterior capsule (AC), and the content of the phaco cassette, were collected during phacoemulsification surgery. The samples were obtained from 12 participants without diabetes mellitus (DM), 11 participants with DM, and 7 participants without DM, with a history of vitrectomy surgery in the past 12 months. The Sp3 protocol (Single-Pot, Solid-Phase, Sample-Preparation) was used for the sample preparation. The recognition and quantification of proteins were carried out with liquid chromatography online with tandem mass spectrometry. The DIA-NN software was applied for the identification and quantification of peptides/proteins. Statistical analysis and data visualization were conducted on Perseus software. Data are available via ProteomeXchange. <b>Results</b>: A very rich atlas of the lens and AH proteome has been generated. Glycosaminoglycan biosynthesis and the non-canonical Wnt receptor signaling pathway were differentially expressed in ARC compared to both the DC and PVC groups. In the PVC group, complement activation was differentially expressed in AH samples, while glutathione metabolism and oxidoreductase activity were differentially expressed in AC samples. Microfilament motor activity, microtubule cytoskeleton organization, and microtubule binding were differentially expressed in the DC and PVC groups in both AH and AC samples. <b>Conclusions</b>: The results of this study expand the existing knowledge on pathways involved in the pathophysiology of cataract, and suggest possible important druggable targets for slower progression or even prevention of cataract.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}