Journal of proteomics最新文献

{"title":"TMT-based quantitative proteomics unveils the protective mechanism of Polygonatum sibiricum polysaccharides on septic acute liver injury","authors":"Linxia Xiao ,&nbsp;Yinuo Ping ,&nbsp;Shangshang Sun ,&nbsp;Ran Xu ,&nbsp;Xinru Zhou ,&nbsp;Hongyan Wu ,&nbsp;Liang Qi","doi":"10.1016/j.jprot.2024.105331","DOIUrl":"10.1016/j.jprot.2024.105331","url":null,"abstract":"<div><div><em>Polygonatum sibiricum</em> polysaccharides (PSP) has been shown to possess multiple pharmacological functions. Our previous study found that PSP could protect against acute liver injury during sepsis via inhibiting inflammatory response. However, the underlying molecular mechanism by which PSP alleviates septic acute liver injury (SALI) remains unknown. Herein, TMT-based quantitative proteomics was utilized to explore the essential pathways and proteins involved in the protective effects of PSP on SALI. The results revealed that 632 and 176 differentially expressed proteins (DEPs) were identified in Model_vs_Control and PSP_vs_Model, respectively. GO annotation showed similar trends, suggesting that these DEPs were primarily involved in the cellular anatomical entity in Cellular Component, the cellular processe and the biological regulation in Biological Process, the binding and the catalytic activity in Molecular Function. Meanwhile, KEGG enrichment analysis implied that four common pathways, including the NF-κB signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway and the Toll-like receptor signaling pathway, were closely associated with the pathogenesis of sepsis among the top 20 remarkably enriched pathways in Model_vs_Control_up and PSP_vs_Model_down. Moreover, the levels of several common DEPs, including TLR2, IKKi, JunB and CXCL9, were validated by WB, which was in line with the results of proteomics. Therefore, the protective effects of PSP on SALI might exert via blocking the above-mentioned inflammation pathways.</div><div>Significance: PSP, recognized as a key component of <em>Polygonatum sibiricum</em>, exhibits a range of pharmacological functions. Our previous study found that PSP could protect against SALI, yet failing to clarify the mechanism of action. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP.</div></div><div><h3>Significance</h3><div>PSP have been identified as the most crucial components of <em>Polygonatum sibiricum</em> with various pharmacological functions. Our previous study found that PSP could protect against SALI, but the mechanism of action remains unknown. To reveal the underlying molecular mechanism involved in the protective effects of PSP on SALI, a TMT-based quantitative proteomic analysis was performed to detect and analyse the DEPs in liver tissue among the control group, the model group and the PSP group in this study. The results provide theoretical references for exploring the action mechanism of drugs and facilitate the comprehensive utilization of PSP.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105331"},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-plex quantitative glycoproteomics using glycan/protein-stable isotope labeling in cell culture","authors":"Peilin Jiang ,&nbsp;Md Abdul Hakim ,&nbsp;Arvin Saffarian Delkhosh ,&nbsp;Parisa Ahmadi ,&nbsp;Yunxiang Li ,&nbsp;Yehia Mechref","doi":"10.1016/j.jprot.2024.105333","DOIUrl":"10.1016/j.jprot.2024.105333","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Alterations in glycoprotein abundance and glycan structures are closely linked to numerous diseases. The quantitative exploration of glycoproteomics is pivotal for biomarker discovery, but comprehensive analysis within biological samples remains challenging due to low abundance, complexity, and lack of universal technology. We developed a multiplex glycoproteomic approach using an LC-ESI-MS platform for direct comparison of glycoproteomic quantitation. Glycopeptides were isotopically labeled during cell culture, achieving high labeling efficiency (≥ 95 %) for both glycans and peptides. Quantitation was validated by mixing the same cell line in a 1:1:1:1 ratio, with mathematical correction applied to deconvolute the ratios. This method proved reliable and was applied to a comparative glycoproteomic study of three breast cancer cell lines (HTB22, MDA-MB-231, MDA-MB-231BR) and one brain cancer cell line (CRL-1620), quantifying glycopeptides from three replicates. The expression of glycopeptides was relatively quantified, and up/down-regulation between cell lines was investigated. This approach provided insights into glycosylation microheterogeneity, crucial for breast cancer brain metastasis research. Benefits include eliminating fluctuations from nano electrospray ionization and reducing analysis time, enabling up to 4-plex profiling in a single injection. Metabolic labeling introduced mass differences at the MS1 level, ensuring increased sensitivity and higher resolution for accurate quantitation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Significance&lt;/h3&gt;&lt;div&gt;Alternations in glycoprotein abundance, changes in glycosylation levels, and variations in glycan structures are closely linked to numerous diseases. The quantitative exploration of glycoproteomics has emerged as a popular area of research for biomarker discovery. However, conducting a comprehensive quantitative analysis of the glycoproteome within biological samples remains challenging due to low abundance, inherent complexities, and the absence of universal quantitative technology. Here, we developed a multiplex glycoproteomic approach using an LC-ESI-MS platform to facilitate direct comparison of glycoproteomic quantitation and enhance throughput. This approach offers benefits such as eliminating quantitative fluctuations arising from nano electrospray ionization (ESI) and reducing analysis time, enabling up to 4-plex glycoproteomic profiling in a single injection. Glycopeptides were stable isotopic labeled during cell culture procedure, attaching to monosaccharides, amino acids, or both. We achieved a high labeling efficiency (≥ 95 %) for both glycans and peptides. Quantitation validation was tested on glycopeptides by mixing the same cell line with 1:1:1:1 ratio. Due to the overlapped isotopes, a mathematical correction was applied to deconvolute the ratio of 4-plex glycopeptides. This method demonstrated quantitative reliability and was successfully applied to a comparative glycoproteomic study of","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105333"},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DSSBU: A novel mass spectrometry-cleavable analogue of the BS3 cross-linker","authors":"Banerjee Swati ,&nbsp;Sýs Jakub ,&nbsp;Machara Aleš ,&nbsp;Junková Petra ,&nbsp;Hubálek Martin","doi":"10.1016/j.jprot.2024.105330","DOIUrl":"10.1016/j.jprot.2024.105330","url":null,"abstract":"<div><div>Protein cross-linking has assumed an irreplaceable role in structural proteomics. Recently, significant efforts have been made to develop novel mass spectrometry (MS)-cleavable reagents. At present, only water-insoluble MS-cleavable cross-linkers are commercially available. However, to comprehensively analyse the various chemical and structural motifs making up proteins, it is necessary to target different protein sites with varying degrees of hydrophilicity. Here we introduce the new MS-cleavable cross-linker disulfodisuccinimidyl dibutyric urea (DSSBU), which we have developed in-house for this purpose. DSSBU contains an <em>N</em>-hydroxysulfosuccinimide (sulfo-NHS) reactive group, so it can serve as a water-soluble counterpart to the widely used cross-linker disuccinimidyl dibutyric urea (DSBU). To investigate the applicability of DSSBU, we compared the efficacy of four similar cross-linkers: bis[sulfosuccinimidyl] suberate (BS³), disuccinimidyl suberate (DSS), DSBU and DSSBU with bovine serum albumin. In addition, we compared the efficacy of DSBU and DSSBU with human haemoglobin. Our results demonstrate that the sulfo-NHS group ensures the superior water solubility of DSSBU and thus negates the need for organic solvents such as dimethyl sulfoxide while preserving the effectivity of urea-based MS-cleavable crosslinkers such as DSBU. Additionally, it makes it possible to target polar regions in proteins. The data gathered are available via ProteomeXchange under identifier <span><span>PXD055284</span><svg><path></path></svg></span>.</div></div><div><h3>Significance</h3><div>We have synthesized the novel protein cross-linker DSSBU, which combines sulfo-NHS ester chemistry with a mass <em>spectrometry-</em>cleavable urea group. This makes DSSBU a water-soluble, MS-cleavable cross-linker that reacts with amino groups. To our knowledge, it is the first cross-linker which combines all three of these characteristics. We have tested the performance of our novel cross-linker on bovine serum albumin, a model widely used by the cross-linking mass spectrometry community, and on human haemoglobin. We have comprehensively assessed the performance of DSSBU and compared its efficacy with that of three other cross-linkers in current use (BS³, DSS and DSBU). We conclude that our novel cross-linker surpasses its MS-non-cleavable analogue BS³ in performance and that its water solubility eliminates the need for organic solvents while its hydrophilicity allows for the targetting of polar regions in proteins. Therefore, it will likely become a significant addition to the portfolio of <em>N</em>-hydroxysuccinimide ester cross-linkers.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105330"},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteo-transcriptomic profiles reveal genetic mechanisms underlying primary hair follicle development in coarse sheep fetal skin","authors":"Dehong Tian ,&nbsp;Wenkui Zhang ,&nbsp;Lei Wang ,&nbsp;Junying Qi ,&nbsp;Teng Xu ,&nbsp;Mingxing Zuo ,&nbsp;Buying Han ,&nbsp;Xue Li ,&nbsp;Kai Zhao","doi":"10.1016/j.jprot.2024.105327","DOIUrl":"10.1016/j.jprot.2024.105327","url":null,"abstract":"<div><div>Long hair trait represents a valuable genetic asset in Qinghai Tibetan sheep, with its quality and yield being contingent upon the characteristics of hair follicles (HFs). This study aims to elucidate the genetic mechanism underlying primary hair follicles (PFs) formation through an integrated analysis of proteomics and transcriptomics. Samples were collected at key stages of fetal HF formation (E65 and E85) for histological observation, revealing significant alterations in the microstructure of PF (E65) during the developmental process. In this study, a comprehensive analysis revealed a total of 217 overlapping genes that exhibited concordant expression patterns at both the proteomic and transcriptomic levels. Furthermore, to ensure the reliability of our findings, we employed parallel response monitoring (PRM) to validate the obtained proteomic data. The protein-protein interaction (PPI) network diagram highlights five hub core proteins (TTN, IGTA2, F2, EGFR, and MYH14). These differentially expressed proteins (DEPs) play crucial roles in metabolic processes, cell adhesion, and diverse biological processes. The potential synergy between transcriptional regulation and post-translational modifications plays a pivotal role in governing the initiation PF development. The findings presented in this study offer innovative insights into the molecular mechanisms underlying HFs generation and establish a robust foundation for targeted breeding strategies aimed at augmenting wool traits in sheep.</div></div><div><h3>Significance</h3><div>The composition of coarse hair primarily consists of long, myelinated fibers originating from primary hair follicles. Sheep fetal skin initiates the formation of primary hair follicles around E65, followed by the development of secondary hair follicles around E85. Conducting differential proteomic and transcriptomic analyses during these developmental stages enhances our understanding of the molecular mechanisms underlying primary hair follicle development and offers valuable insights for sustainable utilization of high-quality germplasm resources.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105327"},"PeriodicalIF":2.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein degradation patterns as biomarkers for post-mortem interval estimation: A comprehensive review of proteomic approaches in forensic science","authors":"Anjali Chhikara,&nbsp;Pallavi Kumari,&nbsp;Jyoti Dalal,&nbsp;Kiran Kumari","doi":"10.1016/j.jprot.2024.105326","DOIUrl":"10.1016/j.jprot.2024.105326","url":null,"abstract":"<div><div>The determination of post-mortem interval (PMI) is a critical process for forensic medical-legal investigations. Proteomic techniques are gaining prominence in analysing forensic biological samples. After death, studying the proteins present in human bodies could be critical in discovering important new biomarkers that can serve as reliable indicators of various factors. A literature review is conducted on estimating PMI through protein degradation analysis using PubMed, NCBI, SCOPUS, Research Gate, Science Direct, and Google Scholar. A total of 32 studies were identified and studied. It is found that the most commonly studied tissue type is the skeleton muscle (15 studies), followed by others. The kinetics of several proteins and proteases were particularly correlated with PMI. Different proteins degrade differently after death: alpha-actinin, GAPDH, and alpha-tubulin breakdown slowly, but meta-vinculin breaks down early. Tropomyosin does not change for a long time after death, up to 10 days. Certain markers had a positive correlation with PMI, meaning that their amount increased as PMI hours increased, while other markers showed a negative correlation, suggesting that their number decreased with time. The level of several biological markers, such as SERBP1, COX7B, and SOD2, changed gradually and consistently as the PMI increased. The information gathered from this analysis provides new opportunities for precise PMI measurements in legal contexts by expanding the research area's use in human skeletal tissue.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105326"},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic integrity of tape-stripped stratum corneum samples endures higher temperatures","authors":"Ali Azimi ,&nbsp;Lauren Faul ,&nbsp;Petrina Chand ,&nbsp;Pablo Fernandez-Penas","doi":"10.1016/j.jprot.2024.105329","DOIUrl":"10.1016/j.jprot.2024.105329","url":null,"abstract":"","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105329"},"PeriodicalIF":2.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydration priming remodels protein abundance and phosphorylation level regulating tolerance to subsequent dehydration or salt stress in creeping bentgrass","authors":"Huizhen Yang ,&nbsp;Yan Yuan ,&nbsp;Zhou Li","doi":"10.1016/j.jprot.2024.105325","DOIUrl":"10.1016/j.jprot.2024.105325","url":null,"abstract":"<div><div>Dehydration priming (DP) induces stress memory which plays a positive role in plant adaptability, but it is not well understood how DP differentially regulates subsequent dehydration (cis priming) or salt (trans priming) tolerance at the post-translational level. Purpose of this study was to identify proteins, phosphorylation levels and sites, and relevant metabolic pathways for DP-induced dehydration or salt tolerance in <em>Agrostis stolonifera</em>. DP-induced differentially regulated proteins (DRPs) were mostly located in the cytoplasm, chloroplast, and cell membrane, and differentially regulated phosphoproteins (DRPPs) were mostly nuclear proteins and cytoplasmic proteins. DP regulated common phosphorylation sites ([SP] and [RxxS]) under dehydration and salt conditions and also individually affected 8 or 11 phosphorylation sites under dehydration or salt stress. DP-regulated DRPPs were mainly rich in glycolysis and glutathione metabolism pathways, RNA splicing, and dynamin family proteins under dehydration stress, whereas DP-regulated salt tolerance was mainly related to chlorophyll metabolism, photosynthesis, MAPK signaling cascade, and ABC transporter I family at the phosphorylation level. In addition, the DP also significantly up-regulated phosphorylation of histones (ATXR3 and SETD1A) in response to subsequent dehydration and salt stress as well as abundances of antioxidant enzymes, dynamin family protein, and KCS6 under dehydration stress or abundances of PETE, HMGA, XTH, and ABCI6 under salt stress, respectively. Transcriptomics analysis further indicated that DP-regulated dehydration or salt tolerance was also related to transcriptional regulation in the early stage. Current results provided better understanding of the role of stress memory in plant adaptability to repeated or crossed stress via post-translational modifications (PTMs).</div></div><div><h3>Significance</h3><div>Recurrent moderate drought may buffer drought legacies in many plant species. When plants were exposed to repeated drought stress, their adaptability to subsequent stress could be enhanced, which is known as “stress memory”. Dehydration priming has been found to be an important approach to induce stress memory. Current results provided better understanding of the role of stress memory in plant adaptability to repeated or crossed stress via post-translational modifications.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105325"},"PeriodicalIF":2.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptomic and proteomic analysis revealed the regulatory role of 5-azacytidine in kenaf salt stress alleviation","authors":"Dengjie Luo ,&nbsp;Zengqiang Li ,&nbsp;Samavia Mubeen ,&nbsp;Muzammal Rehman ,&nbsp;Shan Cao ,&nbsp;Caijin Wang ,&nbsp;Jiao Yue ,&nbsp;Jiao Pan ,&nbsp;Gang Jin ,&nbsp;Ru Li ,&nbsp;Tao Chen ,&nbsp;Peng Chen","doi":"10.1016/j.jprot.2024.105328","DOIUrl":"10.1016/j.jprot.2024.105328","url":null,"abstract":"<div><div>Salinity stress limits agricultural production. The DNA methyltransferase inhibitor, 5-azacitidine (5-azaC), plays a role in plant abiotic stress regulation, but its molecular basis in mediating salinity tolerance in kenaf remains unclear. To investigate the effects on 5-azaC on alleviating salt stress, kenaf seedlings were pre-treated with 0, 50, 100, 150, and 200 μM 5-azaC and then exposed to 150 mM NaCl in a nutrient solution. Physiological, transcriptomic, and proteomic analyses were conducted on the root system to understand the regulatory mechanism of 5-azaC (comparing 5-azaC150 and control group 5-azaC0) under salt stress. The results indicated that 5-azaC significantly mitigated salt stress in kenaf by activating the antioxidant system, reducing reactive oxygen species (ROS), and increasing starch, soluble sugars, and adenosine triphosphate (ATP) content. A total of 14,348 differentially expressed genes (DEGs) and 313 differentially abundant proteins (DAPs) were identified. Combined proteomic and transcriptomic analysis revealed 27 DEGs/DAPs, with jointly up-regulated proteins (genes) including <em>HcTHI1</em>, <em>HcBGLU11</em>, and <em>HcCBL1</em>, and jointly down-regulated proteins (genes) including <em>HcGAPDH</em>, <em>HcSS</em>, and <em>HcPP2C52</em>. Overexpression and virus-induced gene silencing (VIGS) of <em>HcPP2C52</em> demonstrated its role as a negative regulator of salt tolerance. These findings provide insights into the regulatory role of 5-azaC in plant responses to abiotic stresses.</div></div><div><h3>Significance</h3><div>The specific molecular mechanism by which 5-azaC affects gene expression and protein activity of kenaf has been revealed, leading to enhanced salt tolerance.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"309 ","pages":"Article 105328"},"PeriodicalIF":2.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing Leishmania infantum-induced resistance to trivalent stibogluconate (SbIII) through deep proteomics","authors":"Adriana Castillo-Castañeda ,&nbsp;Luz H. Patiño ,&nbsp;Antonio Muro ,&nbsp;Julio López ,&nbsp;Raúl Manzano ,&nbsp;Juan David Ramírez","doi":"10.1016/j.jprot.2024.105323","DOIUrl":"10.1016/j.jprot.2024.105323","url":null,"abstract":"&lt;div&gt;&lt;div&gt;&lt;em&gt;Leishmania infantum&lt;/em&gt; belongs to the &lt;em&gt;L. donovani&lt;/em&gt; complex, which includes species associated with visceral leishmaniasis. Traditionally, antimonial compounds have served as the primary antiparasitic treatment for all clinical forms of leishmaniasis. However, the global spread of resistance to these compounds has posed a significant challenge in the treatment in some regions. In this study, we aimed to investigate resistance to trivalent sodium stibogluconate &lt;em&gt;in vitro&lt;/em&gt; using promastigotes from a wild strain of &lt;em&gt;L. infantum&lt;/em&gt;. We compared the growth rates and proteomic profiles of wild-type and resistant line conducting label-free quantitative mass spectrometry-based proteomic analyses. Statistical and bioinformatics analyses were employed to evaluate the significance of protein concentration changes, protein identity annotation, GO term analysis, biosynthetic pathways, and protein-protein interactions. Our findings revealed that the resistant line displayed a notable reduction in growth rate. Proteomic data unveiled similar protein concentrations per cell in both groups but with differing molecule copy numbers. We identified 165 proteins with increased concentration, these were associated with transcription and translation activities, lipid metabolism, energy metabolism, and peroxisome biogenesis. In the decreased protein groups were 56 proteins linked to metal acquisition and metabolism, particularly iron. These results suggest a novel perspective on antimonial resistance, highlighting the importance of post-transcriptional and post-translational regulation, alongside energy expenditure compensation and alterations in organelle membrane lipid composition in antimonial-resistant parasites. Overall, our study provides insights into the proteomic profile of stibogluconate-resistant strain, contributing to our general understanding of the complex landscape of antiparasitic resistance in &lt;em&gt;L. infantum&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Significance&lt;/h3&gt;&lt;div&gt;Species within the &lt;em&gt;Leishmania donovani&lt;/em&gt; complex are implicated in cases of visceral leishmaniasis in the world. &lt;em&gt;Leishmania infantum&lt;/em&gt; is a species that predominates in regions spanning the Mediterranean Basin, the Middle East, Central Asia, South and Central America. Antimonials were the first treatment for leishmaniasis, however in the last decades, the resistance has emerged in subregions like India, where it is not a therapeutic option. In contrast, sodium stibogluconate (SbIII) remains the first-line treatment in the Americas. Unfortunately, the emergence of resistance has outpaced the development of new therapeutic options, thereby becoming a critical point in the struggle against the disease. In this study we performed an in-depth proteomic analysis with liquid chromatography mass-mass spectrometry (LC-MS/MS) on &lt;em&gt;L. infantum&lt;/em&gt; with Sb-induced resistance &lt;em&gt;in vitro&lt;/em&gt;. Results showed a complex proteomic adaptation in the resistant line, ","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"309 ","pages":"Article 105323"},"PeriodicalIF":2.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of potential drug targets for Glaucoma by plasma proteome screening","authors":"Zhiqi Wang ,&nbsp;Huanyu Zhou ,&nbsp;Fei Wang ,&nbsp;Haishan Huang","doi":"10.1016/j.jprot.2024.105324","DOIUrl":"10.1016/j.jprot.2024.105324","url":null,"abstract":"<div><h3>Background</h3><div>Glaucoma is the leading cause of irreversible blindness. However, the current available treatment methods are still unsatisfactory. Therefore, the exploration of new drug targets for the treatment of glaucoma is of paramount importance.</div></div><div><h3>Methods</h3><div>We conducted two-sample Mendelian randomization (MR) using plasma protein quantitative trait loci (pQTL) data from two datasets (<em>n</em> = 734, <em>n</em> = 4907) and their instrumental variables to investigate the causal relationship between plasma proteins and glaucoma. The analysis was validated by replacing the exposure and outcome cohorts. Additionally, we utilized protein-protein interaction networks to assess the associations between these potential drug targets and existing drug targets.</div></div><div><h3>Results</h3><div>Through two-sample Mendelian randomization analysis, we identified causal relationships between Glaucoma and the following proteins: AZU1, OBP2B, ENPP5, INPP5B, KREMEN1, LYPLAL1, and PTPRJ. External validation confirmed the protective effect of LYPLAL1 on Glaucoma, while ENPP5, KREMEN1, and PTPRJ increased the risk of Glaucoma. Reverse MR and Steiger filtering did not indicate any reverse causal associations of the aforementioned proteins with Glaucoma.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates a causal impact of ENPP5, KREMEN1, PTPRJ, and LYPLAL1 on the risk of Glaucoma. These findings suggest that these four proteins may serve as promising drug targets for Glaucoma treatment.</div></div><div><h3>Significance</h3><div>Currently, the pharmacological treatment of glaucoma primarily focuses on lowering intraocular pressure, which has its limitations. Targeted therapy is a personalized treatment approach that aims to inhibit or block the development and progression of diseases such as cancer and inflammation by selectively acting on specific biomolecules or signaling pathways. Our research employs a two-sample Mendelian randomization (MR) method, integrating a large amount of GWAS and pQTL data to perform MR analysis. This has enabled us to explore several plasma proteins as potential drug targets for glaucoma, providing direction and a research foundation for future investigations into glaucoma drug targets.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"310 ","pages":"Article 105324"},"PeriodicalIF":2.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}