Journal of Proteome Research最新文献

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Combining Native Mass Spectrometry and Proteomics to Differentiate and Map the Metalloform Landscape in Metallothioneins. 结合原生质谱法和蛋白质组学来区分和绘制金属硫蛋白中的金属形态图。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-12 DOI: 10.1021/acs.jproteome.4c00271
Manuel David Peris-Díaz, Alicja Orzeł, Sylwia Wu, Karolina Mosna, Perdita E Barran, Artur Krężel
{"title":"Combining Native Mass Spectrometry and Proteomics to Differentiate and Map the Metalloform Landscape in Metallothioneins.","authors":"Manuel David Peris-Díaz, Alicja Orzeł, Sylwia Wu, Karolina Mosna, Perdita E Barran, Artur Krężel","doi":"10.1021/acs.jproteome.4c00271","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00271","url":null,"abstract":"<p><p>Within the intricate landscape of the proteome, approximately 30% of all proteins bind metal ions. This repertoire is even larger when considering all the different forms of a protein, known as proteoforms. Here, we propose the term \"metalloforms\" to refer to different structural or functional variations of a protein resulting from the binding of various hetero- or homogeneous metal ions. Using human Cu(I)/Zn(II)-metallothionein-3 as a representative model, we developed a chemical proteomics strategy to simultaneously differentiate and map Zn(II) and Cu(I) metal binding sites. In the first labeling step, <i>N</i>-ethylmaleimide reacts with Cysteine (Cys), resulting in the dissociation of all Zn(II) ions while Cu(I) remains bound to the protein. In the second labeling step, iodoacetamide is utilized to label Cu(I)-bound Cys residues. Native mass spectrometry (MS) was used to determine the metal/labeling protein stoichiometries, while bottom-up/top-down MS was used to map the Cys-labeled residues. Next, we used a developed methodology to interrogate an isolated rabbit liver metallothionein fraction containing three metallothionein-2 isoforms and multiple Cd(II)/Zn(II) metalloforms. The approach detailed in this study thus holds the potential to decode the metalloproteoform diversity within other proteins.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588933","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}
引用次数: 0
Data Independent Acquisition Mass Spectrometry Enhanced Personalized Glycosylation Profiling of Haptoglobin in Hepatocellular Carcinoma. 独立数据采集质谱法增强了肝细胞癌中巯基蛋白的个性化糖基化分析。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-12 DOI: 10.1021/acs.jproteome.4c00227
Tiara Pradita, Yi-Ju Chen, Tung-Hung Su, Kun-Hao Chang, Pei-Jer Chen, Yu-Ju Chen
{"title":"Data Independent Acquisition Mass Spectrometry Enhanced Personalized Glycosylation Profiling of Haptoglobin in Hepatocellular Carcinoma.","authors":"Tiara Pradita, Yi-Ju Chen, Tung-Hung Su, Kun-Hao Chang, Pei-Jer Chen, Yu-Ju Chen","doi":"10.1021/acs.jproteome.4c00227","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00227","url":null,"abstract":"<p><p>Aberrant glycosylation has gained significant interest for biomarker discovery. However, low detectability, complex glycan structures, and heterogeneity present challenges in glycoprotein assay development. Using haptoglobin (Hp) as a model, we developed an integrated platform combining functionalized magnetic nanoparticles and zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) for highly specific glycopeptide enrichment, followed by a data-independent acquisition (DIA) strategy to establish a deep cancer-specific Hp-glycosylation profile in hepatitis B virus (HBV, <i>n</i> = 5) and hepatocellular carcinoma (HCC, <i>n</i> = 5) patients. The DIA strategy established one of the deepest Hp-glycosylation landscapes (1029 glycopeptides, 130 glycans) across serum samples, including 54 glycopeptides exclusively detected in HCC patients. Additionally, single-shot DIA searches against a DIA-based spectral library outperformed the DDA approach by 2-3-fold glycopeptide coverage across patients. Among the four N-glycan sites on Hp (N-184, N-207, N-211, N-241), the total glycan type distribution revealed significantly enhanced detection of combined fucosylated-sialylated glycans, which were the most dominant glycoforms identified in HCC patients. Quantitation analysis revealed 48 glycopeptides significantly enriched in HCC (<i>p</i> < 0.05), including a hybrid monosialylated triantennary glycopeptide on the N-184 site with nearly none-to-all elevation to differentiate HCC from the HBV group (HCC/HBV ratio: 2462 ± 766, <i>p</i> < 0.05). In summary, DIA-MS presents an unbiased and comprehensive alternative for targeted glycoproteomics to guide discovery and validation of glyco-biomarkers.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588934","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}
引用次数: 0
Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis. 特应性皮炎患者在杜匹单抗治疗前和治疗结束时通过皮肤开流微灌注收集的间质液中炎症介质和代谢组的特征。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-10 DOI: 10.1021/acs.jproteome.4c00153
Fernanda Monedeiro, Barbara Ehall, Katrin Tiffner, Anita Eberl, Eva Svehlikova, Barbara Prietl, Verena Pfeifer, Julia Senekowitsch, Anu Remm, Ana Rebane, Christoph Magnes, Thomas Pieber, Frank Sinner, Thomas Birngruber
{"title":"Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis.","authors":"Fernanda Monedeiro, Barbara Ehall, Katrin Tiffner, Anita Eberl, Eva Svehlikova, Barbara Prietl, Verena Pfeifer, Julia Senekowitsch, Anu Remm, Ana Rebane, Christoph Magnes, Thomas Pieber, Frank Sinner, Thomas Birngruber","doi":"10.1021/acs.jproteome.4c00153","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00153","url":null,"abstract":"<p><p>Dupilumab is a monoclonal antibody approved for the treatment of atopic dermatitis (AD); however, its effects on molecular, cellular, and immunological levels remain to be elucidated. In this study, blood and dermal interstitial fluid (ISF) from nonlesional (NL) and lesional (L) skin were collected from eight patients with moderate to severe AD, before (visit 2-v2) and at the end of a 16-week treatment with dupilumab (visit 10-v10). Clinical treatment effect was demonstrated by significantly decreased AD severity scores at the end of treatment. At v10 versus v2, the percentages of CD4+ interleukin-producing cells showed a decreasing trend in ISF L and NL, unbound IL-4 levels in plasma were increased, IL-5 levels in ISF L reduced, and levels of factors involved in anti-inflammatory pathways and re-epithelization increased. At v2, ISF L showed that AD lesions might have altered amino acid pathways and lipid signaling compared to ISF NL. At v10, ISF L exhibited raised levels of long- and very-long-chain fatty acids and lipids compared to v2. Furthermore, dupilumab administration caused reduced expression of miR-155-5p and miR-378a-3p in ISF L. In conclusion, results from the present study provided novel knowledge by linking local immune and metabolic alterations to AD pathogenesis and treatment response.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578159","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}
引用次数: 0
Venomics and Peptidomics of Palearctic Vipers: A Clade-Wide Analysis of Seven Taxa of the Genera Vipera, Montivipera, Macrovipera, and Daboia across Türkiye. 古北区蝰蛇的毒液组学和肽组学:对土耳其境内蝰蛇属、蒙蝰属、大蝰属和达博亚属七个类群的全族分析。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-09 DOI: 10.1021/acs.jproteome.4c00171
Maik Damm, Mert Karış, Daniel Petras, Ayse Nalbantsoy, Bayram Göçmen, Roderich D Süssmuth
{"title":"Venomics and Peptidomics of Palearctic Vipers: A Clade-Wide Analysis of Seven Taxa of the Genera <i>Vipera</i>, <i>Montivipera</i>, <i>Macrovipera</i>, and <i>Daboia</i> across Türkiye.","authors":"Maik Damm, Mert Karış, Daniel Petras, Ayse Nalbantsoy, Bayram Göçmen, Roderich D Süssmuth","doi":"10.1021/acs.jproteome.4c00171","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00171","url":null,"abstract":"<p><p>Snake venom variations are a crucial factor to understand the consequences of snakebite envenoming worldwide, and therefore it is important to know about toxin composition alterations between taxa. Palearctic vipers of the genera <i>Vipera</i>, <i>Montivipera</i>, <i>Macrovipera,</i> and <i>Daboia</i> have high medical impacts across the Old World. One hotspot for their occurrence and diversity is Türkiye, located on the border between continents, but many of their venoms remain still understudied. Here, we present the venom compositions of seven Turkish viper taxa. By complementary mass spectrometry-based bottom-up and top-down workflows, the venom profiles were investigated on proteomics and peptidomics level. This study includes the first venom descriptions of <i>Vipera berus barani</i>, <i>Vipera darevskii</i>, <i>Montivipera bulgardaghica albizona,</i> and <i>Montivipera xanthina</i>, as well as the first snake venomics profiles of Turkish <i>Macrovipera lebetinus obtusa</i>, and <i>Daboia palaestinae</i>, including an in-depth reanalysis of <i>M. bulgardaghica bulgardaghica</i> venom. Additionally, we identified the modular consensus sequence pEXW(PZ)<sub>1-2</sub>P(EI)/(KV)PPLE for bradykinin-potentiating peptides in viper venoms. For better insights into variations and potential impacts of medical significance, the venoms were compared against other Palearctic viper proteomes, including the first genus-wide <i>Montivipera</i> venom comparison. This will help the risk assessment of snakebite envenoming by these vipers and aid in predicting the venoms' pathophysiology and clinical treatments.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557406","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}
引用次数: 0
Improving Proteomic Identification Using Narrow Isolation Windows with Zeno SWATH Data-Independent Acquisition. 利用 Zeno SWATH 数据独立采集技术的窄分离窗口改进蛋白质组鉴定。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-09 DOI: 10.1021/acs.jproteome.4c00149
Kongxin Gu, Haruka Kumabe, Takumi Yamamoto, Naoto Tashiro, Takeshi Masuda, Shingo Ito, Sumio Ohtsuki
{"title":"Improving Proteomic Identification Using Narrow Isolation Windows with Zeno SWATH Data-Independent Acquisition.","authors":"Kongxin Gu, Haruka Kumabe, Takumi Yamamoto, Naoto Tashiro, Takeshi Masuda, Shingo Ito, Sumio Ohtsuki","doi":"10.1021/acs.jproteome.4c00149","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00149","url":null,"abstract":"<p><p>Data-independent acquisition (DIA) techniques such as sequential window acquisition of all theoretical mass spectra (SWATH) acquisition have emerged as the preferred strategies for proteomic analyses. Our study optimized the SWATH-DIA method using a narrow isolation window placement approach, improving its proteomic performance. We optimized the acquisition parameter combinations of narrow isolation windows with different widths (1.9 and 2.9 Da) on a ZenoTOF 7600 (Sciex); the acquired data were analyzed using DIA-NN (version 1.8.1). Narrow SWATH (nSWATH) identified 5916 and 7719 protein groups on the digested peptides, corresponding to 400 ng of protein from mouse liver and HEK293T cells, respectively, improving identification by 7.52 and 4.99%, respectively, compared to conventional SWATH. The median coefficient of variation of the quantified values was less than 6%. We further analyzed 200 ng of benchmark samples comprising peptides from known ratios of<i>Escherichia coli</i>, yeast, and human peptides using nSWATH. Consequently, it achieved accuracy and precision comparable to those of conventional SWATH, identifying an average of 95,456 precursors and 9342 protein groups across three benchmark samples, representing 12.6 and 9.63% improved identification compared to conventional SWATH. The nSWATH method improved identification at various loading amounts of benchmark samples, identifying 40.7% more protein groups at 25 ng. These results demonstrate the improved performance of nSWATH, contributing to the acquisition of deeper proteomic data from complex biological samples.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557404","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}
引用次数: 0
Are We There Yet? Assessing the Readiness of Single-Cell Proteomics to Answer Biological Hypotheses. 我们到了吗?评估单细胞蛋白质组学在解答生物学假设方面的准备情况。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-09 DOI: 10.1021/acs.jproteome.4c00091
Alyssa A Nitz, Jose Humberto Giraldez Chavez, Zachary G Eliason, Samuel H Payne
{"title":"Are We There Yet? Assessing the Readiness of Single-Cell Proteomics to Answer Biological Hypotheses.","authors":"Alyssa A Nitz, Jose Humberto Giraldez Chavez, Zachary G Eliason, Samuel H Payne","doi":"10.1021/acs.jproteome.4c00091","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00091","url":null,"abstract":"<p><p>Single-cell analysis is an active area of research in many fields of biology. Measurements at single-cell resolution allow researchers to study diverse populations without losing biologically meaningful information to sample averages. Many technologies have been used to study single cells, including mass spectrometry-based single-cell proteomics (SCP). SCP has seen a lot of growth over the past couple of years through improvements in data acquisition and analysis, leading to greater proteomic depth. Because method development has been the main focus in SCP, biological applications have been sprinkled in only as proof-of-concept. However, SCP methods now provide significant coverage of the proteome and have been implemented in many laboratories. Thus, a primary question to address in our community is whether the current state of technology is ready for widespread adoption for biological inquiry. In this Perspective, we examine the potential for SCP in three thematic areas of biological investigation: cell annotation, developmental trajectories, and spatial mapping. We identify that the primary limitation of SCP is sample throughput. As proteome depth has been the primary target for method development to date, we advocate for a change in focus to facilitate measuring tens of thousands of single-cell proteomes to enable biological applications beyond proof-of-concept.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561971","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}
引用次数: 0
The Spatial Extracellular Proteomic Tumor Microenvironment Distinguishes Molecular Subtypes of Hepatocellular Carcinoma. 空间细胞外蛋白质组肿瘤微环境可区分肝细胞癌的分子亚型
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-09 DOI: 10.1021/acs.jproteome.4c00099
Jade K Macdonald, Harrison B Taylor, Mengjun Wang, Andrew Delacourt, Christin Edge, David N Lewin, Naoto Kubota, Naoto Fujiwara, Fahmida Rasha, Cesia A Marquez, Atsushi Ono, Shiro Oka, Kazuaki Chayama, Sara Lewis, Bachir Taouli, Myron Schwartz, M Isabel Fiel, Richard R Drake, Yujin Hoshida, Anand S Mehta, Peggi M Angel
{"title":"The Spatial Extracellular Proteomic Tumor Microenvironment Distinguishes Molecular Subtypes of Hepatocellular Carcinoma.","authors":"Jade K Macdonald, Harrison B Taylor, Mengjun Wang, Andrew Delacourt, Christin Edge, David N Lewin, Naoto Kubota, Naoto Fujiwara, Fahmida Rasha, Cesia A Marquez, Atsushi Ono, Shiro Oka, Kazuaki Chayama, Sara Lewis, Bachir Taouli, Myron Schwartz, M Isabel Fiel, Richard R Drake, Yujin Hoshida, Anand S Mehta, Peggi M Angel","doi":"10.1021/acs.jproteome.4c00099","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00099","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) mortality rates continue to increase faster than those of other cancer types due to high heterogeneity, which limits diagnosis and treatment. Pathological and molecular subtyping have identified that HCC tumors with poor outcomes are characterized by intratumoral collagenous accumulation. However, the translational and post-translational regulation of tumor collagen, which is critical to the outcome, remains largely unknown. Here, we investigate the spatial extracellular proteome to understand the differences associated with HCC tumors defined by Hoshida transcriptomic subtypes of poor outcome (Subtype 1; S1; <i>n</i> = 12) and better outcome (Subtype 3; S3; <i>n</i> = 24) that show differential stroma-regulated pathways. Collagen-targeted mass spectrometry imaging (MSI) with the same-tissue reference libraries, built from untargeted and targeted LC-MS/MS was used to spatially define the extracellular microenvironment from clinically-characterized, formalin-fixed, paraffin-embedded tissue sections. Collagen α-1(I) chain domains for discoidin-domain receptor and integrin binding showed distinctive spatial distribution within the tumor microenvironment. Hydroxylated proline (HYP)-containing peptides from the triple helical regions of fibrillar collagens distinguished S1 from S3 tumors. Exploratory machine learning on multiple peptides extracted from the tumor regions could distinguish S1 and S3 tumors (with an area under the receiver operating curve of ≥0.98; 95% confidence intervals between 0.976 and 1.00; and accuracies above 94%). An overall finding was that the extracellular microenvironment has a high potential to predict clinically relevant outcomes in HCC.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557405","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}
引用次数: 0
Impact of Surfactants on Cumulative Trypsin Activity in Bottom-Up Proteome Analysis. 自下而上蛋白质组分析中表面活性剂对累积胰蛋白酶活性的影响
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-07 DOI: 10.1021/acs.jproteome.4c00162
Jessica L Nickerson, Liam V Sheridan, Alan A Doucette
{"title":"Impact of Surfactants on Cumulative Trypsin Activity in Bottom-Up Proteome Analysis.","authors":"Jessica L Nickerson, Liam V Sheridan, Alan A Doucette","doi":"10.1021/acs.jproteome.4c00162","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00162","url":null,"abstract":"<p><p>Trypsin digestion plays a pivotal role in successful bottom-up peptide characterization and quantitation. While denaturants are often incorporated to enhance protein solubility, surfactants are recognized to inhibit enzyme activity. However, several reports have suggested that incorporating surfactants or other solvent additives may enhance digestion and MS detection. Here, we assess the impacts of ionic surfactants on cumulative trypsin activity and subsequently evaluate the total digestion efficiency of a proteome mixture by quantitative MS. Although low surfactant concentrations, such as 0.01% SDS or 0.2% SDC, significantly enhanced the initial trypsin activity (by 14 or 42%, respectively), time course assays revealed accelerated enzyme deactivation, evident by 10- or 40-fold reductions in trypsin activity half-life at these respective surfactant concentrations. Despite enhanced initial tryptic activity, quantitative MS analysis of a common liver proteome extract, digested with various surfactants (0.01 or 0.1% SDS, 0.5% SDC), consistently revealed decreased peptide counts and signal intensity, indicative of a lower digestion efficiency compared to a nonsurfactant control. Furthermore, including detergents for digestion did not improve the detection of membrane proteins, nor hydrophobic peptides. These results stress the importance of assessing cumulative enzyme activity when optimizing the digestion of a proteome mixture, particularly in the presence of denaturants.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553569","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}
引用次数: 0
Multiomics to Characterize the Molecular Events Underlying Impaired Glucose Tolerance in FXR-Knockout Mice. 多组学分析 FXR 基因敲除小鼠葡萄糖耐受性受损的分子事件。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-05 DOI: 10.1021/acs.jproteome.3c00475
Yun-Chung Hsiao, Yifei Yang, Chih-Wei Liu, Jingya Peng, Jiahao Feng, Haoduo Zhao, Taylor Teitelbaum, Kun Lu
{"title":"Multiomics to Characterize the Molecular Events Underlying Impaired Glucose Tolerance in FXR-Knockout Mice.","authors":"Yun-Chung Hsiao, Yifei Yang, Chih-Wei Liu, Jingya Peng, Jiahao Feng, Haoduo Zhao, Taylor Teitelbaum, Kun Lu","doi":"10.1021/acs.jproteome.3c00475","DOIUrl":"https://doi.org/10.1021/acs.jproteome.3c00475","url":null,"abstract":"<p><p>The prevalence of different metabolic syndromes has grown globally, and the farnesoid X receptor (FXR), a metabolic homeostat for glucose, lipid, and bile acid metabolisms, may serve an important role in the progression of metabolic disorders. Glucose intolerance by FXR deficiency was previously reported and observed in our study, but the underlying biology remained unclear. To investigate the ambiguity, we collected the nontargeted profiles of the fecal metaproteome, serum metabolome, and liver proteome in <i>Fxr</i>-null (<i>Fxr</i><sup><i>-/-</i></sup>) and wild-type (WT) mice with LC-HRMS. FXR deficiency showed a global impact on the different molecular levels we monitored, suggesting its serious disruption in the gut microbiota, hepatic metabolism, and circulating biomolecules. The network and enrichment analyses of the dysregulated metabolites and proteins suggested the perturbation of carbohydrate and lipid metabolism by FXR deficiency. <i>Fxr</i><sup><i>-/-</i></sup> mice presented lower levels of hepatic proteins involved in glycogenesis. The impairment of glycogenesis by an FXR deficiency may leave glucose to accumulate in the circulation, which may deteriorate glucose tolerance. Lipid metabolism was dysregulated by FXR deficiency in a structural-dependent manner. Fatty acid β-oxidations were alleviated, but cholesterol metabolism was promoted by an FXR deficiency. Together, we explored the molecular events associated with glucose intolerance by impaired FXR with integrated novel multiomic data.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141532820","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}
引用次数: 0
Two-Step Enrichment Facilitates Background Reduction for Proteomic Analysis of Lysosomes. 两步富集法有助于降低溶酶体蛋白质组分析的背景。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2024-07-05 DOI: 10.1021/acs.jproteome.4c00053
Sara Bonini, Dominic Winter
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