Journal of proteomics最新文献

{"title":"New potential susceptibility factors contributing to tomato bacterial spot disease","authors":"Lucas José de Sousa ,&nbsp;Ivonaldo Reis Santos ,&nbsp;Isabelle Souza Luz ,&nbsp;Daiane Gonzaga Ribeiro ,&nbsp;Osmundo Brilhante de Oliveira-Neto ,&nbsp;Wagner Fontes ,&nbsp;Luiz Eduardo Bassay Blum ,&nbsp;Angela Mehta","doi":"10.1016/j.jprot.2025.105387","DOIUrl":"10.1016/j.jprot.2025.105387","url":null,"abstract":"<div><div>The label-free shotgun proteomics analysis carried out in this study aimed to understand the molecular mechanisms that contribute towards tomato susceptibility to <em>Xanthomonas euvesicatoria</em> pv. <em>perforans</em> (<em>Xep</em>). To achieve this, comparative proteomics was performed on susceptible inoculated plants with the bacterium and the control group (saline solution) at 24 and 48 h after inoculation (hai). The results revealed that most of the identified proteins showed increased abundance in the infected group and were classified into different gene ontology groups. Eight of these proteins were related to susceptibility in other pathosystems, suggesting their potential involvement in the development of bacterial spot in tomato. Some of these proteins are involved in the negative regulation of salicylic acid, PR proteins and reactive oxygen species (ROS), as well as contributing to the acquisition of sugars by the pathogen. The results obtained in this study provided us with valuable information for understanding the molecular mechanisms that lead to tomato susceptibility to <em>Xep</em> and will help in developing tomato cultivars resistant to bacterial spot.</div></div><div><h3>Significance</h3><div>Our proteomic study of tomato plants during infection by <em>Xep</em> allowed for the identification of potential proteins that contribute to bacterial spot tomato disease development. These proteins can act in different ways to favor the pathogen, such as the negative modulation of phytohormones involved in plant defense, the inhibition of PR proteins and reactive oxygen species, as well as to collaborate in the acquisition of sugar for pathogen nutrition.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"314 ","pages":"Article 105387"},"PeriodicalIF":2.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039406","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":"2025: A historic moment for proteomics!","authors":"Jean Armengaud","doi":"10.1016/j.jprot.2025.105385","DOIUrl":"10.1016/j.jprot.2025.105385","url":null,"abstract":"","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"313 ","pages":"Article 105385"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978902","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":"Effects of periodontal disease on the proteomic profile of the periodontal ligament","authors":"Maria Eduarda Scordamaia Lopes ,&nbsp;Camila Chierici Marcantonio ,&nbsp;Cristiane Ribeiro Salmon ,&nbsp;Luciana Souto Mofatto ,&nbsp;Francisco Humberto Nociti Junior ,&nbsp;Sigrun Eick ,&nbsp;James Deschner ,&nbsp;Joni Augusto Cirelli ,&nbsp;Andressa Vilas Boas Nogueira","doi":"10.1016/j.jprot.2025.105384","DOIUrl":"10.1016/j.jprot.2025.105384","url":null,"abstract":"<div><div>Periodontal disease affects over 1 billion people globally. This study investigated how periodontitis affects the protein profile of the periodontal ligament (PDL) in rats. Eight Holtzman rats were divided into control and experimental periodontitis groups. The PDL was isolated using laser capture microdissection and protein extracts were analyzed by mass spectrometry. Data analysis utilized specialized software, and Gene Ontology enrichment analysis identified significant protein functions. The data are available <em>via</em> ProteomeXchange with identifier <span><span>PXD055817</span><svg><path></path></svg></span>. Proteins such as SerpinB1, C5, and Lgals3 were validated through immunohistochemistry, and their gene expression was examined in an <em>in vitro</em> human PDL cell line. This study identified 1326 proteins, with 156 unique to the control group, 294 unique to the periodontitis group, and 876 common to both groups. Enrichment analysis revealed that proteins associated with the regulation of enzyme activity and RNA binding were significantly represented in the periodontitis group. There were increased levels of SerpinB1, C5, and Lgals3 in the periodontitis group based on proteomic and immunohistochemical analyses. Furthermore, these targets showed increased gene expression in stimulated human PDL cells. This study provides insights into the periodontitis-related alterations in the protein composition of the PDL and PDL cells, identifying both novel and previously known disease-associated proteins.</div></div><div><h3>Significance</h3><div>The periodontal ligament plays a crucial role in oral functions by providing structural support to the tooth. Due to the presence of undifferentiated mesenchymal cells, research into its regenerative capacity is ongoing. Pathological conditions can affect these functions and protein composition. Currently, there is a lack of comprehensive research specifically focusing on evaluating the periodontal ligament in both healthy and diseased states. This pioneering study screened for protein alterations and the mechanisms related to periodontitis. The possibility of using proteomic analysis to evaluate the protein alterations that occur in periodontitis, a disease with a high global incidence, could provide therapeutic targets and new biomarkers for future clinical studies.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"314 ","pages":"Article 105384"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971407","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":"The effect of thermal stress on the X-organ/sinus gland proteome of the estuarine blue crab Callinectes sapidus during the intermolt and premolt stages","authors":"José Thalles Lacerda ,&nbsp;Daniela Dantas David ,&nbsp;Ana Maria L. Castrucci","doi":"10.1016/j.jprot.2025.105382","DOIUrl":"10.1016/j.jprot.2025.105382","url":null,"abstract":"<div><div>Survival of brachyuran crabs is temperature-dependent and thermal stress promotes changes during molting. We aimed to decipher the impact of thermal stresses on the X-organ/sinus gland (XO/SG) complex, a temperature-sensitive neuroendocrine tissue involved in the molting regulation of <em>Callinectes sapidus</em> during the intermolt and premolt phases. We employed a proteogenomic approach using specimens subjected to control (24 °C), cold (19 °C), and heat (29 °C) temperatures. A total of 1463 protein groups with at least two unique peptides were identified and quantified. <em>C. sapidus</em> in the premolt stage exposed to the cold condition exhibited a proteome closely resembling that of the intermolt stage, as evidenced by measurements of circulating ecdysteroid levels. Compared to the intermolt at control temperature, the premolt stage exhibited increased energy metabolism, structural changes in the cuticle mediated by chitin metabolism and glycoproteins, biosynthesis of methyl farnesoate (MF), and elevated tissue levels of molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH), indicating lower secretion rates. Heat temperature (29 °C) seems to induce mitochondrial metabolism in the intermolt XO/SG, while cold temperature elicited a delayed molt cycle in the premolt phase, marked by reduced tissue levels of CHH, indicating increased secretion and Y-organ (YO) inhibition, and decreased MF production (reduced YO stimulation).</div></div><div><h3>Significance statement</h3><div>Temperature plays a pivotal role in regulating the metabolism, growth, molting, reproduction, and survival of crabs, such as the blue crab (<em>Callinectes sapidus</em>). Despite the blue crab's significance on both economic and ecological realms, there has been a notable lack of molecular information related to this species and therefore a gap in our knowledge of the blue crab's molecular makeup and genetic diversity. This research established a comprehensive proteome landscape to elucidate the molecular and functional changes in the XO/SG complex involved in the molting process of <em>C. sapidus</em>, and how thermal stresses significantly influence biotransformation processes. Utilizing a proteogenomics approach with multi-round homologous database analysis, we have generated a highly accurate protein repertoire with at least two unique peptide of XO/SG tissue proteome. This resource will be invaluable for future molecular analyses of this species. Our findings demonstrate that thermal stresses induced specific modifications in the XO/SG tissue, depending on the molt cycle phase. Temperature-mediated responses influences the biological processes, enhancing the functional morphogenesis and comprehensive metabolic adaptations on molting cycle supported by a relationship between the XO/SG tissue proteome and circulating ecdysteroid levels.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"313 ","pages":"Article 105382"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971408","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":"Proteome changes during the germination and early seedling development of carnauba palm (Copernicia prunifera) under skotomorphogenic conditions","authors":"Sheheryar Sheheryar ,&nbsp;Francisco A.S.A. Carioca ,&nbsp;Ítalo A.C. Coutinho ,&nbsp;Yara M. Silva ,&nbsp;Gilberto B. Domont ,&nbsp;Fábio C.S. Nogueira ,&nbsp;Francisco A.P. Campos","doi":"10.1016/j.jprot.2025.105386","DOIUrl":"10.1016/j.jprot.2025.105386","url":null,"abstract":"<div><div>We analyze the proteome changes during the development of the carnauba palm (<em>Copernicia prunifera</em>) seedlings under skotomorphogenic conditions, by separating the embryo into its two components: haustorium (HA) and cotyledonary petiole (CP) and established the descriptive and quantitative proteomes of these tissues across four developmental stages. 5205 proteins were identified in HA and 6028 in CP. These proteomes are rich in proteins known to maintain the skotomorphogenic state, and in a complete set of proteins involved in cellular respiration and biosynthesis of secondary metabolites. The quantitative analysis employing a label-free approach revealed that 583 proteins in HA and 383 in CP were differentially abundant, with 251 proteins shared between the datasets. The results showed that HA participates in the digestion of food reserves present in HA itself and in the endosperm, acting as a conduit of nitrogen and carbon sources for the growing embryo axis. Among the differentially abundant proteins in the CP, we identified the presence of proteins from the cellular metabolism and proteins involved in the hydrolysis of food reserves such as starch and proteins. This indicates that the CP, in addition to the endosperm and HA, serves as a source of food reserves for the embryo axis.</div></div><div><h3>Significance</h3><div>Our results also reveal the differential regulation of specific proteins involved in reactive oxygen species scavenging, cell wall remodeling, respiratory metabolism, and protein repair in seeds and seedlings of <em>C. prunifera</em>. These findings have broad implications for understanding the energy metabolism that drives the transition from seed to seedling.</div><div>For this study, we employed state-of-the-art proteomic techniques, including quantitative mass spectrometry and bioinformatic analysis, that allowed us to create a large dataset that will be a valuable resource for future research on the physiological and biochemical aspects of skotomorphogenesis, photomorphogenesis, and the transition between these states.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"313 ","pages":"Article 105386"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971131","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":"A combined proteomic and metabolomic analysis of the early aborted embryonic tissues with maternal COVID-19 infection","authors":"Ling Ling ,&nbsp;Guiqin Xu ,&nbsp;Miao Fang ,&nbsp;Jianquan Chen ,&nbsp;Ming Gong ,&nbsp;TianMing Wang ,&nbsp;Rong Ju ,&nbsp;Sipei Nie","doi":"10.1016/j.jprot.2025.105383","DOIUrl":"10.1016/j.jprot.2025.105383","url":null,"abstract":"<div><div>COVID-19 still spreads worldwide, and repeated infections are hard to avoid. Maternal infection during pregnancy is associated with adverse maternal and neonatal outcomes. Our study used a multi-omics profiling method to explore the proteome and metabolome alteration in early embryonic development after COVID-19 infection. A total of 30 chorionic tissues after artificial abortion (15 infection and 15 no-infection samples) were collected, and the UHPLC-MS/MS and LC-MS/MS were applied in the present study. As a result, 311 significantly differentially expressed proteins were identified. The function annotations revealed that the thermogenesis pathway is the most significantly enriched signaling pathway; PRKAG2, IGF1R, and RPS6KB2 were identified as the hub proteins. There were 359 metabolites significantly altered after infection. The functional annotations revealed that amino acid metabolism was significantly affected, especially beta-alanine metabolism, glutamate metabolism, and histidine metabolism pathways. The metabolites in ovarian steroidogenesis showed a down-regulating trend in the infection group. Finally, we combined the results of proteins and metabolomics analysis. The biosynthesis of the cofactors pathway was identified as significantly enriched in both proteomics and metabolomics datasets. Our findings provide a network of protein regulation and metabolite perturbation during early embryonic development with COVID-19 infection. Our findings can provide valuable insights for further exploration of the complex mechanism of COVID-19-associated pregnancy complications and outcomes.</div></div><div><h3>Significance</h3><div>COVID-19 has developed into the most prominent and deadliest pandemic respiratory disease in the world, and repeated infections are complicated to avoid. COVID-19 infection during pregnancy increases the risk of adverse maternal and neonatal outcomes, such as preterm birth and stillbirth. However, previous studies mainly focused on its effect on pregnant women, such as the clinical characteristics and gestation outcomes. There is no relevant report about the effects of virus infection on embryos in early pregnancy. The effects of COVID-19 infection changes of the proteins and metabolites during early embryonic development are undefined. Our findings provide an association between protein regulation, metabolite perturbation, and COVID-19 infection, which can provide valuable insights for further exploration of the complex mechanism COVID-19 COVID-19-associated pregnancy complications and adverse pregnancy outcomes.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"313 ","pages":"Article 105383"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965497","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":"Multi-omics analysis reveals the regulatory mechanism of branching development in Quercus fabri","authors":"Shifa Xiong ,&nbsp;Liwen Wu ,&nbsp;Yicun Chen ,&nbsp;Xiang Shi ,&nbsp;Yangdong Wang","doi":"10.1016/j.jprot.2024.105373","DOIUrl":"10.1016/j.jprot.2024.105373","url":null,"abstract":"<div><div>The ability of axillary meristems to form axillary buds and subsequently develop into branches is influenced by phytohormones, environmental conditions, and genetic factors. The main trunk of <em>Quercus fabri</em> is prone to branching, which not only impacts the appearance and density of the wood and significantly reduces the yield rate. This study conducted transcriptomic, proteomic, and metabolomic analyses on three stages of axillary bud development in <em>Q. fabri</em>. A total of 12,888 differentially expressed genes (DEGs), 8193 differentially accumulated proteins (DAPs), and 1788 differentially accumulated metabolites (DAMs) were identified through comparisons among the stages and subjected to multi-omics joint analysis. Conduct interaction network analysis on DEGs and DAPs to identify the significant transcription factor family (AP2/ERF) involved in the regulation of axillary bud development. Furthermore, KEGG enrichment analysis of DEGs, DAPs and DAMs indicated significant enrichment in plant hormone signaling pathways. The analysis of endogenous hormone levels and qRT-PCR results for pathway genes demonstrated that the expression levels of IAA and tZ significantly increased during late developmental stages, whereas the expression levels of ABA, ACC and JA significantly decreased. In summary, these findings contribute to a comprehensive understanding of the regulatory networks underlying the branching development of <em>Q. fabri</em>.</div></div><div><h3>Significance</h3><div><em>Q. fabri</em> exhibits robust vegetative growth, and its primary trunk is prone to branching, significantly influencing the wood yield rate. Through a joint analysis of transcriptomics, proteomics, and metabolomics, we comprehensively examined the regulatory network governing the axillary bud development of <em>Q. fabri</em>. Our findings revealed the crucial roles of the AP2/ERF transcription factor family and plant hormone signal transduction pathways in branch development. These insights contribute to a deeper understanding of the mechanisms regulating branch development.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"313 ","pages":"Article 105373"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950537","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":"Molecular insights into myelomeningocele via proteomic analysis of amniotic fluid","authors":"Lucie Guilbaud ,&nbsp;Kévin Roger ,&nbsp;Andree Schmidt ,&nbsp;Cerina Chhuon ,&nbsp;Stephan Breimann ,&nbsp;Joanna Lipecka ,&nbsp;Sophie Dreux ,&nbsp;Stephan A. Müller ,&nbsp;Michel Zérah ,&nbsp;Jérôme Larghero ,&nbsp;Jean-Marie Jouannic ,&nbsp;Stefan F. Lichtenthaler ,&nbsp;Ida C. Guerrera","doi":"10.1016/j.jprot.2024.105372","DOIUrl":"10.1016/j.jprot.2024.105372","url":null,"abstract":"<div><div>Despite numerous studies on fetal therapy for myelomeningoceles (MMC), the pathophysiology of this malformation remains poorly understood.</div><div>This study aimed to analyze the biochemical profile and proteome of amniotic fluid (AF) supernatants from MMC fetuses to explore the prenatal pathophysiology.</div><div>Biochemical analysis of 61 AF samples from MMC fetuses was compared with 45 healthy fetuses' samples. Proteome analysis was conducted in 18 MMC and 18 healthy singleton fetuses, and in 5 dichorionic pregnancies with MMC fetuses and their healthy co-twins. ELISA tests were used to validate proteome results.</div><div>Biochemical analysis revealed anal incontinence in 37 % of MMC cases, absent in controls (<em>p</em> &lt; 0.0001). Proteomics identified 2453 quantified proteins with 39 significantly up-regulated and 10 down-regulated in the MMC group. Up-regulated proteins included ectodomains of CHL1, APLP1, SEZ6, SEZ6L, known targets of the protease BACE1. We explored the overlap of neonatal cerebrospinal fluid (CSF) and AF proteome and highlighted 411 proteins in common, mostly upregulated in MMC AF compared to controls.</div><div>Our study thoroughly characterizes the AF proteome and reveals numerous proteins to be changed as a consequence of MMC. Many of these proteins are typical constituents of CSF. No difference in AF inflammation markers were observed between MMC and healthy fetuses.</div></div><div><h3>Significance</h3><div>This study provides good evidence that neuroepithelial destruction in MMC is independent of inflammation or presumed meconium toxicity.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"313 ","pages":"Article 105372"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950535","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":"A comprehensive proteomic analysis reveals novel inflammatory biomarkers in intracranial aneurysms","authors":"Siqi Chen ,&nbsp;Ziliang Hu ,&nbsp;Mingyue Zhao ,&nbsp;Jie Sun ,&nbsp;Sheng Nie ,&nbsp;Xiang Gao ,&nbsp;Yi Huang","doi":"10.1016/j.jprot.2025.105374","DOIUrl":"10.1016/j.jprot.2025.105374","url":null,"abstract":"<div><div>Inflammation is a complex factor in the pathogenesis of intracranial aneurysms (IA), but its specific cellular inflammatory factors remain uncertain. We collected two cohorts and measured the representation of vascular inflammation-related proteins using the Olink CVD II Vascular Inflammation Panel. We subsequently validated our findings using ELISA and RT-qPCR. Our proteomic analysis identified 11 vascular inflammation-related markers that were significantly differentially represented between the IA and control groups. These markers were implicated in leukocyte migration, immune response, triglyceride and lipoprotein metabolism, acute phase response, T cell regulation, and several key biological pathways, including PPAR, HIF-1, cytokine-cytokine interactions, and PI3K-AKT signaling. Further validation with ELISA and RT-qPCR confirmed the differential representation of IL6, PTX3, LPL, and OLR1 between the two groups. Notably, a combination marker incorporating these four factors demonstrated high diagnostic potential for the early detection of IA. Our study has identified a set of informative biomarkers (IL6, PTX3, LPL, and OLR1) that could be valuable for the early diagnosis of IA. Importantly, this is the first report of significantly elevated OLR1 representation in the plasma of IA patients. Further investigation into the role of OLR1 in the pathogenesis of IA is warranted.</div></div><div><h3>Significance</h3><div>This study significantly advances our understanding of the molecular mechanisms underlying intracranial aneurysm (IA) pathogenesis. By identifying a panel of novel biomarkers, including the previously unreported elevated expression of OLR1 in IA patients, we provide crucial insights into the inflammatory processes involved in aneurysm formation and development. These findings have important clinical implications, as the identified biomarkers could serve as valuable tools for early diagnosis and potentially targeted therapeutic interventions. Furthermore, the study highlights the complex interplay of inflammatory pathways in IA, suggesting that a multi-faceted approach may be necessary for effective management.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"313 ","pages":"Article 105374"},"PeriodicalIF":2.8,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080457","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":"Cardio-metabolic and cytoskeletal proteomic signatures differentiate stress hypersensitivity in dystrophin-deficient mdx mice","authors":"Gretel S. Major ,&nbsp;Craig W. Herbold ,&nbsp;Flora Cheng ,&nbsp;Albert Lee ,&nbsp;Shuzhao Zhuang ,&nbsp;Aaron P. Russell ,&nbsp;Angus Lindsay","doi":"10.1016/j.jprot.2024.105371","DOIUrl":"10.1016/j.jprot.2024.105371","url":null,"abstract":"<div><div>Extreme heterogeneity exists in the hypersensitive stress response exhibited by the dystrophin-deficient <em>mdx</em> mouse model of Duchenne muscular dystrophy. Because stress hypersensitivity can impact dystrophic phenotypes, this research aimed to understand the peripheral pathways driving this inter-individual variability. Male and female <em>mdx</em> mice were phenotypically stratified into “stress-resistant” or “stress-sensitive” groups based on their response to two laboratory stressors. Quantitative proteomics of striated muscle revealed that stress-resistant females were most dissimilar from all other groups, with over 250 proteins differentially regulated with stress hypersensitivity. Males showed less proteomic variation with stress hypersensitivity; however, these changes were associated with pathway enrichment. In the heart, stress-sensitive males had significant enrichment of pathways related to mitochondrial ATP synthesis, suggesting that increased cardio-metabolic capacity is associated with stress hypersensitivity in male <em>mdx</em> mice. In both sexes, stress hypersensitivity was associated with greater expression of beta-actin-like protein 2, indicative of altered cytoskeletal organisation. Despite identifying proteomic signatures associated with stress hypersensitivity, these did not correlate with differences in the serum metabolome acutely after a stressor. These data suggest that the heterogeneity in stress hypersensitivity in <em>mdx</em> mice is partially driven by cytoskeletal organisation, but that sex-specific cardio-metabolic reprogramming may also underpin this phenotype.</div></div><div><h3>Significance</h3><div>Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease which is associated with a premature loss of ambulation and neurocognitive dysfunction. The hypersensitive stress response in DMD is a heterogeneous phenotype which is poorly understood. This study provided the first investigation of the peripheral mechanisms regulating the hypersensitive stress response by undertaking multi-omics analysis of phenotypically stratified <em>mdx</em> mice. Variations in behaviour and the striated muscle proteomic profiles suggest that cardio-metabolic remodelling and cytoskeletal organisation may contribute to this phenotype. This research offers significant insights into understanding how peripheral dystrophin deficiency relates to the cognitive abnormalities seen in patients with DMD.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"312 ","pages":"Article 105371"},"PeriodicalIF":2.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895528","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}