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DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance.
IF 4
Proteomes Pub Date : 2025-01-20 DOI: 10.3390/proteomes13010006
Shantanu Gupta, Daner A Silveira, José Carlos M Mombach, Ronaldo F Hashimoto
{"title":"DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance.","authors":"Shantanu Gupta, Daner A Silveira, José Carlos M Mombach, Ronaldo F Hashimoto","doi":"10.3390/proteomes13010006","DOIUrl":"10.3390/proteomes13010006","url":null,"abstract":"<p><p>The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by lipid peroxidation. Post-translational modifications of p53 generate proteoforms that significantly enhance its functional diversity in regulating these mechanisms. A key target in this process is the cystine/glutamate transporter (xCT), which is essential for redox balance and ferroptosis resistance. Additionally, p53-induced miR-34c-5p suppresses cancer cell proliferation and drug resistance by modulating Myc, an oncogene further influenced by non-coding RNAs like circular RNA NOTCH1 (CricNOTCH1) and long non-coding RNA MALAT1. However, the exact role of these molecules in ferroptosis remains unclear. To address this, we introduce the first dynamic Boolean model that delineates the influence of these ncRNAs and p53 on ferroptosis, apoptosis, and senescence within the DDR context. Validated through gain- and loss-of-function perturbations, our model closely aligns with experimental observations in cancers such as oral squamous cell carcinoma, nasopharyngeal carcinoma, and osteosarcoma. The model identifies crucial positive feedback loops (CricNOTCH1/miR-34c/Myc, MALAT1/miR-34c/Myc, and Myc/xCT) and highlights the therapeutic potential of using p53 proteoforms and ncRNAs to combat drug resistance and induce cancer cell death.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing Biomedicine: Proteomics and Metabolomics in Action.
IF 4
Proteomes Pub Date : 2025-01-16 DOI: 10.3390/proteomes13010005
Michele Costanzo, Marianna Caterino, Lucia Santorelli
{"title":"Enhancing Biomedicine: Proteomics and Metabolomics in Action.","authors":"Michele Costanzo, Marianna Caterino, Lucia Santorelli","doi":"10.3390/proteomes13010005","DOIUrl":"10.3390/proteomes13010005","url":null,"abstract":"<p><p>The rapid and substantial advancements in proteomic and metabolomic technologies have revolutionized our ability to investigate biological systems [...].</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of Proteoforms Related to Nelumbo nucifera Flower Petaloid Through Proteogenomic Strategy.
IF 4
Proteomes Pub Date : 2025-01-15 DOI: 10.3390/proteomes13010004
Zhongyuan Lin, Jiantao Shu, Yu Qin, Dingding Cao, Jiao Deng, Pingfang Yang
{"title":"Identification of Proteoforms Related to <i>Nelumbo nucifera</i> Flower Petaloid Through Proteogenomic Strategy.","authors":"Zhongyuan Lin, Jiantao Shu, Yu Qin, Dingding Cao, Jiao Deng, Pingfang Yang","doi":"10.3390/proteomes13010004","DOIUrl":"10.3390/proteomes13010004","url":null,"abstract":"<p><p><i>Nelumbo nucifera</i> is an aquatic plant with a high ornamental value due to its flower. Despite the release of several versions of the lotus genome, its annotation remains inefficient, which makes it difficult to obtain a more comprehensive knowledge when -omic studies are applied to understand the different biological processes. Focusing on the petaloid of the lotus flower, we conducted a comparative proteomic analysis among five major floral organs. The proteogenomic strategy was applied to analyze the mass spectrometry data in order to dig out novel proteoforms that are involved in the petaloids of the lotus flower. The results revealed that a total of 4863 proteins corresponding to novel genes were identified, with 227 containing single amino acid variants (SAAVs), and 72 originating from alternative splicing (AS) genes. In addition, a range of post-translational modifications (PTMs) events were also identified in lotus. Through functional annotation and homology analysis with 24 closely related plant species, we identified five candidate proteins associated with floral organ development, which were not identified by ordinary proteomic analysis. This study not only provides new insights into understanding the mechanism of petaloids in lotus but is also helpful in identifying new proteoforms to improve the annotation of the lotus genome.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis.
IF 4
Proteomes Pub Date : 2025-01-13 DOI: 10.3390/proteomes13010003
Fei Wang, Liang Jin, Xue Wang, Baoliang Cui, Yingli Yang, Lori Duggan, Annette Schwartz Sterman, Sarah M Lloyd, Lisa A Hazelwood, Neha Chaudhary, Bhupinder Bawa, Lucy A Phillips, Yupeng He, Yu Tian
{"title":"Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis.","authors":"Fei Wang, Liang Jin, Xue Wang, Baoliang Cui, Yingli Yang, Lori Duggan, Annette Schwartz Sterman, Sarah M Lloyd, Lisa A Hazelwood, Neha Chaudhary, Bhupinder Bawa, Lucy A Phillips, Yupeng He, Yu Tian","doi":"10.3390/proteomes13010003","DOIUrl":"10.3390/proteomes13010003","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis is identifying cell types associated with histopathological regions, particularly local fibrosis centers known as fibroblast foci. To address this, we integrated published spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) transcriptomics and adopted the Query method and the Overlap method to determine cell type enrichments in histopathological regions. Distinct fibroblast cell types are highly associated with fibroblast foci, and transitional alveolar type 2 and aberrant KRT5-/KRT17+ (KRT: keratin) epithelial cells are associated with morphologically normal alveoli in human IPF lungs. Furthermore, we employed laser capture microdissection-directed mass spectrometry to profile proteins. By comparing with another published similar dataset, common differentially expressed proteins and enriched pathways related to ECM structure organization and collagen processing were identified in fibroblast foci. Importantly, cell type enrichment results from innovative spatial proteomics and scRNA-seq data integration accord with those from spatial transcriptomics and scRNA-seq data integration, supporting the capability and versatility of the entire approach. In summary, we integrated spatial multi-omics with scRNA-seq data to identify disease-associated cell types and potential targets for novel therapies in IPF intervention. The approach can be further applied to other disease areas characterized by spatial heterogeneity.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HRAMS Proteomics Insights on the Anti-Filarial Effect of Ocimum sanctum: Implications in Phytochemical-Based Drug-Targeting and Designing.
IF 4
Proteomes Pub Date : 2024-12-27 DOI: 10.3390/proteomes13010002
Ayushi Mishra, Vipin Kumar, Sunil Kumar, HariOm Singh, Anchal Singh
{"title":"HRAMS Proteomics Insights on the Anti-Filarial Effect of <i>Ocimum sanctum</i>: Implications in Phytochemical-Based Drug-Targeting and Designing.","authors":"Ayushi Mishra, Vipin Kumar, Sunil Kumar, HariOm Singh, Anchal Singh","doi":"10.3390/proteomes13010002","DOIUrl":"10.3390/proteomes13010002","url":null,"abstract":"<p><p>Lymphatic filariasis (LF) continues to impact 657 million individuals worldwide, resulting in lifelong and chronic impairment. The prevalent anti-filarial medications-DEC, albendazole, and ivermectin-exhibit limited adulticidal efficacy. Despite ongoing LF eradication programs, novel therapeutic strategies are essential for effective control. This study examines the mechanism of action of <i>Ocimum sanctum</i> on the filarial parasites <i>Setaria cervi</i> via a synergistic biochemical and proteomics methodology. The ethanolic extract of <i>Ocimum sanctum</i> (EOS) demonstrated potential anti-filarial action in the MTT reduction experiment, with an LC<sub>50</sub> value of 197.24 µg/mL. After EOS treatment, an elevation in lipid peroxidation (51.92%), protein carbonylation (48.99%), and NADPH oxidase (88.88%) activity, along with a reduction in glutathione (GSH) (-39.23%), glutathione reductase (GR) (-60.17%), and glutathione S transferase (GST) (-50.48%) activity, was observed. The 2D gel electrophoresis identified 20 decreased and 11 increased protein spots in the EOS-treated parasites relative to the control group. Additionally, in drug docking analysis, the EOS bioactive substances ursolic acid, rutin, and rosmarinic acid show a significant binding affinity with the principal differentially expressed proteins. This paper demonstrates, for the first time, that the anti-filarial efficacy of EOS is primarily facilitated by its impact on energy metabolism, antioxidant mechanisms, and stress response systems of the parasites.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phospho-Proteomics Analysis of Early Response to X-Ray Irradiation Reveals Molecular Mechanism Potentially Related to U251 Cell Radioresistance.
IF 4
Proteomes Pub Date : 2024-12-25 DOI: 10.3390/proteomes13010001
Ousseynou Ben Diouf, Antoine Gilbert, Benoit Bernay, Randi G Syljuåsen, Mihaela Tudor, Mihaela Temelie, Diana I Savu, Mamadou Soumboundou, Cheikh Sall, François Chevalier
{"title":"Phospho-Proteomics Analysis of Early Response to X-Ray Irradiation Reveals Molecular Mechanism Potentially Related to U251 Cell Radioresistance.","authors":"Ousseynou Ben Diouf, Antoine Gilbert, Benoit Bernay, Randi G Syljuåsen, Mihaela Tudor, Mihaela Temelie, Diana I Savu, Mamadou Soumboundou, Cheikh Sall, François Chevalier","doi":"10.3390/proteomes13010001","DOIUrl":"10.3390/proteomes13010001","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a devastating malignant brain tumor with a poor prognosis. GBM is associated with radioresistance. Post-translational modifications (PTMs) such as protein phosphorylation can play an important role in the cellular response to radiation. To better understand the early cellular activities after radiation in GBM, we carried out a phospho-proteomic study on the U251 cell line 3 h after X-ray irradiation (6Gy) and on non-irradiated cells. Our study showed a strong modification of proteoform phosphorylation in response to radiation. We found 453 differentially expressed phosphopeptides (DEPs), with 211 being upregulated and 242 being downregulated. A GO enrichment analysis of DEPs showed a strong enrichment of the signaling pathways involved in DNA damage response after irradiation and categorized them into biological processes (BPs), cellular components (CCs) and molecular functions (MFs). Certain accessions such as BRCA1, MDC1, H2AX, MDC1, TP53BP1 were dynamically altered in our fraction and are highly associated with the signaling pathways enriched after radiation.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"13 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Affinity-Enriched Plasma Proteomics for Biomarker Discovery in Abdominal Aortic Aneurysms. 利用亲和富集血浆蛋白质组学发现腹主动脉瘤的生物标志物。
IF 4
Proteomes Pub Date : 2024-12-09 DOI: 10.3390/proteomes12040037
Nicolai Bjødstrup Palstrøm, Kristian Boje Nielsen, Amanda Jessica Campbell, Mette Soerensen, Lars Melholt Rasmussen, Jes Sanddal Lindholt, Hans Christian Beck
{"title":"Affinity-Enriched Plasma Proteomics for Biomarker Discovery in Abdominal Aortic Aneurysms.","authors":"Nicolai Bjødstrup Palstrøm, Kristian Boje Nielsen, Amanda Jessica Campbell, Mette Soerensen, Lars Melholt Rasmussen, Jes Sanddal Lindholt, Hans Christian Beck","doi":"10.3390/proteomes12040037","DOIUrl":"10.3390/proteomes12040037","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by the weakening and dilation of the abdominal aorta. Few diagnostic biomarkers have been proposed for this condition. We performed mass spectrometry-based proteomics analysis of affinity-enriched plasma from 45 patients with AAA and 45 matched controls to identify changes to the plasma proteome and potential diagnostic biomarkers. Gene ontology analysis revealed a significant upregulation of the proteins involved in inflammation, coagulation, and extracellular matrix in AAA patients, while proteins related to angiogenesis were among those downregulated. Using recursive feature elimination, we identified a subset of 10 significantly regulated proteins that were highly predictive of AAA. A random forest classifier trained on these proteins achieved an area under the curve (AUC) of 0.93 [95% CI: 0.91-0.95] using cross-validation. Further validation in a larger cohort is necessary to confirm these results.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"12 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11678615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep Proteome Coverage of Microglia Using a Streamlined Data-Independent Acquisition-Based Proteomic Workflow: Method Consideration for a Phenotypically Diverse Cell Type. 使用流线型数据独立获取的基于蛋白质组学工作流程的小胶质细胞深度蛋白质组覆盖:表型多样化细胞类型的方法考虑。
IF 4
Proteomes Pub Date : 2024-11-27 DOI: 10.3390/proteomes12040035
Jessica Wohlfahrt, Jennifer Guergues, Stanley M Stevens
{"title":"Deep Proteome Coverage of Microglia Using a Streamlined Data-Independent Acquisition-Based Proteomic Workflow: Method Consideration for a Phenotypically Diverse Cell Type.","authors":"Jessica Wohlfahrt, Jennifer Guergues, Stanley M Stevens","doi":"10.3390/proteomes12040035","DOIUrl":"10.3390/proteomes12040035","url":null,"abstract":"<p><p>As the primary innate immune cells of the brain, microglia play a key role in various homeostatic and disease-related processes. To carry out their numerous functions, microglia adopt a wide range of phenotypic states. The proteomic landscape represents a more accurate molecular representation of these phenotypes; however, microglia present unique challenges for proteomic analysis. This study implemented a streamlined liquid- and gas-phase fractionation method with data-dependent acquisition (DDA) and parallel accumulation-serial fragmentation (PASEF) analysis on a TIMS-TOF instrument to compile a comprehensive protein library obtained from adult-derived, immortalized mouse microglia with low starting material (10 µg). The empirical library consisted of 9140 microglial proteins and was utilized to identify an average of 7264 proteins/run from single-shot, data-independent acquisition (DIA)-based analysis microglial cell lysate digest (200 ng). Additionally, a predicted library facilitated the identification of 7519 average proteins/run from the same DIA data, revealing complementary coverage compared with the empirical library and collectively increasing coverage to approximately 8000 proteins. Importantly, several microglia-relevant pathways were uniquely identified with the empirical library approach. Overall, we report a simplified, reproducible approach to address the proteome complexity of microglia using low sample input and show the importance of library optimization for this phenotypically diverse cell type.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"12 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11679481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peptidomic Analysis Reveals Temperature-Dependent Proteolysis in Rainbow Trout (Oncorhynchus mykiss) Meat During Sous-Vide Cooking. 肽组学分析揭示了虹鳟鱼肉在真空烹调过程中的温度依赖性蛋白水解。
IF 4
Proteomes Pub Date : 2024-11-27 DOI: 10.3390/proteomes12040036
Miyu Sakuyama, Yuri Kominami, Hideki Ushio
{"title":"Peptidomic Analysis Reveals Temperature-Dependent Proteolysis in Rainbow Trout (<i>Oncorhynchus mykiss</i>) Meat During Sous-Vide Cooking.","authors":"Miyu Sakuyama, Yuri Kominami, Hideki Ushio","doi":"10.3390/proteomes12040036","DOIUrl":"10.3390/proteomes12040036","url":null,"abstract":"<p><p>Sous vide, a cooking method that involves vacuum-sealed fish at low temperatures, yields a uniquely tender, easily flaked texture. Previous research on sous-vide tenderization has focused on thermal protein denaturation. On the other hand, the contribution of proteases, activated at low temperatures in fish meat, has been suggested. However, the details of protein degradation remain unclear. This study employed SDS-PAGE/immunoblot and peptidomic analysis of rainbow trout to assess proteolysis during sous-vide cooking. The results from SDS-PAGE and immunoblot analysis indicated reduced thermal aggregation of sarcoplasmic proteins and increased depolymerization of actin under low-temperature cooking conditions. A comparison of the peptidome showed that the proteolysis of myofibrillar proteins was accelerated during sous-vide cooking, with distinct proteases potentially activated at different cooking temperatures. Terminome analysis revealed the contribution of specific proteases at higher temperatures in rainbow trout. The results of this study demonstrate the thermal denaturation of sarcoplasmic proteins and proteolysis of myofibrillar proteins in rainbow trout meat during sous-vide cooking and its temperature dependence. The methodology in the present study could provide insights into the optimization of cooking conditions for different fish species, potentially leading to improved texture and quality of sous-vide products.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"12 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11679362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Non-Linear Profile of Aging: U-Shaped Expression of Myostatin, Follistatin and Intermediate Signals in a Longitudinal In Vitro Murine Cell Sarcopenia Model. 衰老的非线性特征:纵向体外小鼠细胞肉质疏松症模型中肌节蛋白、软骨素和中间信号的 U 型表达。
IF 4
Proteomes Pub Date : 2024-11-22 DOI: 10.3390/proteomes12040034
Janire Alonso-Puyo, Oihane Izagirre-Fernandez, Olatz Crende, Jesús Seco-Calvo, Ainhoa Fernandez-Atutxa, Diego Fernandez-Lazaro, Patricia Garcia-Gallastegi, Begoña Sanz
{"title":"The Non-Linear Profile of Aging: U-Shaped Expression of Myostatin, Follistatin and Intermediate Signals in a Longitudinal In Vitro Murine Cell Sarcopenia Model.","authors":"Janire Alonso-Puyo, Oihane Izagirre-Fernandez, Olatz Crende, Jesús Seco-Calvo, Ainhoa Fernandez-Atutxa, Diego Fernandez-Lazaro, Patricia Garcia-Gallastegi, Begoña Sanz","doi":"10.3390/proteomes12040034","DOIUrl":"10.3390/proteomes12040034","url":null,"abstract":"<p><p>Sarcopenia is linked to the decline in muscle mass, strength and function during aging. It affects the quality and life expectancy and can lead to dependence. The biological process underlying sarcopenia is unclear, but the proteins myostatin and follistatin are involved in the balance between muscle breakdown and synthesis. While myostatin promotes muscle breakdown, follistatin promotes muscle growth, but several works have shown an inconsistent association of these proteins with aging-related parameters in serum of older people. We aimed to know the evolution of these putative sarcopenia biomarkers along muscle aging in an in vitro model. We created and phenotyped a longitudinal murine model (C2C12 cells). Then, we analyzed the protein and genetic expression of myostatin and follistatin as well as the signaling pathway regulators mTOR and RPS6KB1. Myostatin and RPS6KB1 showed a similar tendency in both protein and genetic expression with aging (basal-up-down). Follistatin, on the other hand, shows the opposite tendency (basal-down-up). Regarding mTOR, the tendencies differ when analyzing proteins (basal-up-down) or genes (basal-down-down). Our work demonstrates a U-shape tendency for myostatin and follistatin and for the signaling pathway regulators. These results could be of the utmost importance when designing further research on seeking molecular biomarkers and/or targets for sarcopenia.</p>","PeriodicalId":20877,"journal":{"name":"Proteomes","volume":"12 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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