Journal of Proteome Research最新文献

{"title":"Proteome Profiling of Experimental Autoimmune Encephalomyelitis Mouse Model and the Effect of a SUMO E1 Inhibitor","authors":"Yingdong Du,&nbsp;Linlin Yang,&nbsp;Xiaoxiao Wang,&nbsp;Na Jiang,&nbsp;Yanting Zhou,&nbsp;Ruibing Chen* and Hongyan Li*,&nbsp;","doi":"10.1021/acs.jproteome.4c0022910.1021/acs.jproteome.4c00229","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00229https://doi.org/10.1021/acs.jproteome.4c00229","url":null,"abstract":"<p >Multiple sclerosis (MS) is one of the most common neurodegenerative diseases, causing demyelination and inflammation in the central nervous system. The pathology of MS has been extensively studied using the experimental autoimmune encephalomyelitis (EAE) mouse model. However, the molecular mechanisms are still largely unclear and require further investigation. In this study, we carried out quantitative proteomic analysis of the brain and spinal cord tissues in mice induced with EAE using a data-independent acquisition strategy and identified 744 differentially regulated proteins in the brain and 741 in the spinal cord. The changed proteins were highly related with phagocytosis, lysosomal enzymes, inflammasome activation, complements, and synaptic loss processes. Moreover, gene set enrichment analysis revealed the elevation of the SUMOylation process in EAE with the increase of SUMOylation-related enzymes and modification targets. Furthermore, to test the possibility of treating MS by targeting SUMOylation, we explored the application of a selective SUMO E1 inhibitor, TAK-981. Intriguingly, TAK-981 suppressed the global SUMOylation level in the brain and significantly alleviated the symptoms of EAE in mice. Our findings contribute to a better understanding of MS pathology, reveal the important role of SUMOylation in disease progression, and demonstrate the potential of the SUMO E1 inhibitor as a novel treatment for MS.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5312–5325 5312–5325"},"PeriodicalIF":3.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850969","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":"Cognitive Impairment Mechanisms in High-Altitude Exposure: Proteomic and Metabolomic Insights","authors":"Qin Zhao,&nbsp;Jinli Meng,&nbsp;Li Feng,&nbsp;Suyuan Wang,&nbsp;Kejin Xiang,&nbsp;Yonghong Huang,&nbsp;Hengyan Li,&nbsp;Xiaomei Li,&nbsp;Xin Hu,&nbsp;Lu Che,&nbsp;Yongxing Fu,&nbsp;Liming Zhao,&nbsp;Yunhong Wu* and Wanlin He*,&nbsp;","doi":"10.1021/acs.jproteome.4c0084110.1021/acs.jproteome.4c00841","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00841https://doi.org/10.1021/acs.jproteome.4c00841","url":null,"abstract":"<p >High-altitude exposure can adversely affect neurocognitive functions; however, the underlying mechanisms remain elusive. Why and how does high-altitude exposure impair neurocognitive functions, particularly sleep? This study seeks to identify the molecular markers and mechanisms involved, with the goal of forming prevention and mitigation strategies for altitude sickness. Using serum proteomics and metabolomics, we analyzed blood samples from 23 Han Chinese plain dwellers before and after six months of high-altitude work in Tibet. The correlation analysis revealed biomarkers associated with cognitive alterations. Six months of high-altitude exposure significantly compromised cognitive function, notably, sleep quality. The key biomarkers implicated include SEPTIN5, PCBP1, STIM1, UBE2L3/I/N, amino acids (<span>l</span>/<span>d</span>-aspartic acid and <span>l</span>-glutamic acid), arachidonic acid, and S1P. Immune and neural signaling were suppressed, with sex-specific differences observed. This study innovatively identified GABA, arachidonic acid, <span>l</span>-glutamic acid, 2-arachidonoyl glycerol, and <span>d</span>-aspartic acid as biomarkers and elucidated the underlying mechanisms contributing to high-altitude-induced neurocognitive decline with a particular focus on sleep disruption. These findings pave the way for developing preventive measures and enhancing adaptation strategies. This study underscores the physiological significance of high-altitude adaptation, raising new questions about sex-specific responses and long-term consequences. It sets the stage for future research exploring individual variability and intervention efficacy.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5586–5599 5586–5599"},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jproteome.4c00841","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850569","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":"Clinical Peptidomics in Acute Leukemias: Current Advances and Future Perspectives","authors":"Danila Felix Coutinho,&nbsp;Túlio Resende Freitas,&nbsp;Ana Carolina Silva Batista,&nbsp;Mariana Torquato Quezadode Magalhães* and Adriano de Paula Sabino*,&nbsp;","doi":"10.1021/acs.jproteome.4c0080710.1021/acs.jproteome.4c00807","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00807https://doi.org/10.1021/acs.jproteome.4c00807","url":null,"abstract":"<p >The study of circulating peptides in the blood offers significant opportunities for diagnosing, stratifying, and managing various diseases. With recent technological advances and the ongoing need to understand complex diseases such as acute leukemias (AL), peptidomic analysis of peripheral blood, especially serum and plasma, has become increasingly important for studying human biology and pathophysiology. Here, we provide insights and perspectives on technological developments and potential clinical applications using widely used peptidomic analysis methods. We discuss examples where peptidomics using serum or plasma has contributed to the understanding of AL. Specifically, we highlight the scarcity of peptidomic studies applied to AL and emphasize the importance of exploring this area, as the few published studies present promising results that can significantly contribute to precision medicine.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5263–5273 5263–5273"},"PeriodicalIF":3.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jproteome.4c00807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850444","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":"Optimized and Robust Workflow for Quantifying the Canonical Histone Ubiquitination Marks H2AK119ub and H2BK120ub by LC–MS/MS","authors":"Mariana Lopes,&nbsp;Peder J. Lund* and Benjamin A. Garcia*,&nbsp;","doi":"10.1021/acs.jproteome.4c0051910.1021/acs.jproteome.4c00519","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00519https://doi.org/10.1021/acs.jproteome.4c00519","url":null,"abstract":"<p >The eukaryotic genome is packaged around histone proteins, which are subject to a myriad of post-translational modifications. By controlling DNA accessibility and the recruitment of protein complexes that mediate chromatin-related processes, these modifications constitute a key mechanism of epigenetic regulation. Since mass spectrometry can easily distinguish between these different modifications, it has become an essential technique in deciphering the histone code. Although robust LC–MS/MS methods are available to analyze modifications on the histone N-terminal tails, routine methods for characterizing ubiquitin marks on histone C-terminal regions, especially H2AK119ub, are less robust. Here, we report the development of a simple workflow for the detection and improved quantification of the canonical histone ubiquitination marks H2AK119ub and H2BK120ub. The method entails a fully tryptic digestion of acid-extracted histones, followed by derivatization with heavy or light propionic anhydride. A pooled sample is then spiked into oppositely labeled single samples as a reference channel for relative quantification, and data is acquired using PRM-based nano-LC–MS/MS. We validated our approach with synthetic peptides as well as treatments known to modulate the levels of H2AK119ub and H2BK120ub. This new method complements existing histone workflows, largely focused on the lysine-rich N-terminal regions, by extending modification analysis to other sequence contexts.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5405–5420 5405–5420"},"PeriodicalIF":3.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842999","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 Shotgun Proteomic-Based Approach with a Q-Exactive Hybrid Quadrupole-Orbitrap High-Resolution Mass Spectrometer for the Assessment of Pesticide Mixture-Induced Neurotoxicity on a 3D-Developed Neurospheroid Model from Human Brain Meningiomas: Identification of Trityl-Post-Translational Modification","authors":"Kaouthar Louati*,&nbsp;Amina Maalej,&nbsp;Fatma Kolsi,&nbsp;Rim Kallel,&nbsp;Yassine Gdoura,&nbsp;Mahdi Borni,&nbsp;Leila Sellami Hakim,&nbsp;Rania Zribi,&nbsp;Sirine Choura,&nbsp;Sami Sayadi,&nbsp;Mohamed Chamkha,&nbsp;Basma Mnif,&nbsp;Zouheir Khemakhem,&nbsp;Tahya Sellami Boudawara,&nbsp;Mohamed Zaher Boudawara,&nbsp;Abderrahman Bouraoui,&nbsp;Jamil Kraiem and Fathi Safta,&nbsp;","doi":"10.1021/acs.jproteome.4c0080410.1021/acs.jproteome.4c00804","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00804https://doi.org/10.1021/acs.jproteome.4c00804","url":null,"abstract":"<p >The widespread use of pesticides, particularly in combinations, has resulted in enhanced hazardous health effects. However, little is known about their molecular mechanism of interactions. The aim of this study was to assess the neurotoxicity effect of pesticides in mixtures by adopting a 3D in vitro developed neurospheroid model, followed by treatment by increased concentrations of pesticides for 24 h and analysis by a shotgun proteomic-based approach with high-resolution tandem mass spectrometry. Three proteins, namely, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), α-enolase, and phosphoglycerate-kinase-1, were selected as key targets in the metabolic process. Only high doses of pesticides mitigated cell-density proliferation with the occurrence of apoptotic cells, which unlikely makes any neurological alterations in environmental regulatory exposures. The proteomic analysis showed that majority of altered proteins were implicated in cell metabolism. De novo peptide sequencing revealed ion losses and adduct formation, namely, a trityl-post-translational modification in the active site of 201-GAPDH protein. The study also highlights the plausible role of pyrethroids to be implicated in the deleterious effects of pesticides in a mixture. To the best of our knowledge, our finding is the first in toxicoproteomics to deeply elucidate pesticides’ molecular interactions and their ability to adduct proteins as a pivotal role in the neurotoxicity mechanism.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5554–5576 5554–5576"},"PeriodicalIF":3.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jproteome.4c00804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842996","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":"Simultaneous Protein Quantitation and Glycosylation Profiling of Antigen-Specific Immunoglobulin G1 in Large Clinical Studies","authors":"Steinar Gijze,&nbsp;Anna Wasynczuk,&nbsp;Leanne van Leeuwen,&nbsp;Marloes Grobben,&nbsp;Marit J. van Gils,&nbsp;Jan Nouta,&nbsp;Wenjun Wang,&nbsp;Virgil ASH Dalm,&nbsp;Hetty Jolink,&nbsp;Manfred Wuhrer and David Falck*,&nbsp;","doi":"10.1021/acs.jproteome.4c0053810.1021/acs.jproteome.4c00538","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00538https://doi.org/10.1021/acs.jproteome.4c00538","url":null,"abstract":"<p >Antibodies have a key role in the immune system, making their characterization essential to biomedical, biopharmaceutical, and clinical research questions. Antibody effector functions are mainly controlled by quantity, subclass, and Fc glycosylation. We describe an integrated method to measure these three critical dimensions simultaneously. The subclass-specific immunoglobulin G (IgG) Fc glycosylation analysis combines immunosorbance with glycopeptide-centered LC-MS detection. For integrated IgG1-specific quantitation, a commercial, stable isotope labeled IgG1 protein standard was spiked into the immunosorbent eluates. Robust quantitation was achieved, relying on a combination of a proteotypic peptide and the most abundant glycopeptides, generated through proteolytic cleavage from a mixture of natural IgG1 and the recombinant IgG1 standard. Method performance was demonstrated in a large coronavirus vaccination cohort at a throughput of 100 samples/day. LC-MS-derived, anti-SARS-CoV-2 spike protein IgG1 concentrations ranged from 100 to 10000 ng/mL and correlated well with a clinically relevant immunoassay. Technical variation was 200 times lower than biological variation; intermediate precision was 44%. In conclusion, we present a method capable of robustly and simultaneously assessing quantity, subclass, and Fc glycosylation of antigen-specific IgG in large clinical studies. This method will facilitate a broader understanding of immune responses, especially the important interplay among the three dimensions.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5600–5605 5600–5605"},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jproteome.4c00538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842848","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":"Correction to “Involvement of Rab6 in the Regulation of Phagocytosis against Virus Infection in Invertebrates”","authors":"Ting Ye,&nbsp;Wen Tang and Xiaobo Zhang*,&nbsp;","doi":"10.1021/acs.jproteome.4c0097910.1021/acs.jproteome.4c00979","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00979https://doi.org/10.1021/acs.jproteome.4c00979","url":null,"abstract":"","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5615–5617 5615–5617"},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842847","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":"Distinct O-Acetylation Patterns of Serum Glycoproteins among Humans, Mice, and Rats","authors":"Didi Liu,&nbsp;Yue Xue,&nbsp;Dan Ding,&nbsp;Bojing Zhu,&nbsp;Jiechen Shen,&nbsp;Zhehui Jin and Shisheng Sun*,&nbsp;","doi":"10.1021/acs.jproteome.4c0065310.1021/acs.jproteome.4c00653","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00653https://doi.org/10.1021/acs.jproteome.4c00653","url":null,"abstract":"<p ><i>O</i>-Acetylation is a significant chemical modification of sialic acids on glycoproteins with diverse biological functions. As two important animal models, mice and rats have been widely used for various biomedical studies. In this study, we show that the sialic acid types and their <i>O</i>-acetylation patterns have large differences among serum glycoproteins of humans, rats, and mice. Based on intact <i>N</i>-glycopeptide analyses, all sialoglycopeptides in human sera were modified by Neu5Ac without any <i>O</i>-acetylation; 90% of sialoglycopeptides in rat sera were also modified by Neu5Ac, with more than 60% that were further <i>O</i>-acetylated. In contrast, 99% of sialoglycopeptides in mouse sera contained Neu5Gc including 12% in <i>O</i>-acetylated forms. Among all <i>O</i>-acetylated <i>N</i>-glycans, rat sera had hybrid glycans fivefold those of mouse sera, while mouse sera contained 5.5-fold core-fucosylated glycans and 4.6–31.5-fold mono-/penta-/hexa-antenna glycans compared to mice. The overall <i>O</i>-acetylation proportions of serum glycoproteins in rats were much higher than those in mice, and diverse <i>O</i>-acetylation proportions also commonly existed at different glycosites of the same glycoproteins. This study enhances our understanding of <i>O</i>-acetylated sialoglycan diversities and underscores the necessity of considering glycosylation profiles when selecting suitable animal models for various biomedical studies.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5511–5519 5511–5519"},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142850088","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":"Autonomous Dissociation-type Selection for Glycoproteomics Using a Real-Time Library Search","authors":"Emmajay Sutherland,&nbsp;Tim S. Veth,&nbsp;William D. Barshop,&nbsp;Jacob H. Russell,&nbsp;Kathryn Kothlow,&nbsp;Jesse D. Canterbury,&nbsp;Christopher Mullen,&nbsp;David Bergen,&nbsp;Jingjing Huang,&nbsp;Vlad Zabrouskov,&nbsp;Romain Huguet,&nbsp;Graeme C. McAlister and Nicholas M. Riley*,&nbsp;","doi":"10.1021/acs.jproteome.4c0072310.1021/acs.jproteome.4c00723","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00723https://doi.org/10.1021/acs.jproteome.4c00723","url":null,"abstract":"<p >Tandem mass spectrometry (MS/MS) is the gold standard for intact glycopeptide identification, enabling peptide sequence elucidation and site-specific localization of glycan compositions. Beam-type collisional activation is generally sufficient for <i>N-</i>glycopeptides, while electron-driven dissociation is crucial for site localization in <i>O-</i>glycopeptides. Modern glycoproteomic methods often employ multiple dissociation techniques within a single LC-MS/MS analysis, but this approach frequently sacrifices sensitivity when analyzing multiple glycopeptide classes simultaneously. Here we explore the utility of intelligent data acquisition for glycoproteomics through real-time library searching (RTLS) to match oxonium ion patterns for on-the-fly selection of the appropriate dissociation method. By matching dissociation method with glycopeptide class, this autonomous dissociation-type selection (ADS) generates equivalent numbers of <i>N-</i>glycopeptide identifications relative to traditional beam-type collisional activation methods while also yielding comparable numbers of site-localized <i>O-</i>glycopeptide identifications relative to conventional electron transfer dissociation-based methods. The ADS approach represents a step forward in glycoproteomics throughput by enabling site-specific characterization of both <i>N-</i>and <i>O-</i>glycopeptides within the same LC-MS/MS acquisition.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5606–5614 5606–5614"},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142842844","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":"Canadian Proteomics: A Journey across the Country Highlights Discovery and Innovation","authors":"Jennifer Geddes-McAlister*,&nbsp; and ,&nbsp;Nicole Hansmeier*,&nbsp;","doi":"10.1021/acs.jproteome.4c0096010.1021/acs.jproteome.4c00960","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00960https://doi.org/10.1021/acs.jproteome.4c00960","url":null,"abstract":"","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"23 12","pages":"5229–5232 5229–5232"},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843150","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}