Value of Label-Free Ubiquitin-Proteomic Analysis on Defining the Protective Mechanism of Valsartan against Doxorubicin-Induced Heart Failure.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2025-01-14 DOI:10.2174/0115680096341637241231111922

Liyuan Zhang, Yujing Zhang, Di Chen, Shujuan Shao, Qin Yu

{"title":"Value of Label-Free Ubiquitin-Proteomic Analysis on Defining the Protective Mechanism of Valsartan against Doxorubicin-Induced Heart Failure.","authors":"Liyuan Zhang, Yujing Zhang, Di Chen, Shujuan Shao, Qin Yu","doi":"10.2174/0115680096341637241231111922","DOIUrl":null,"url":null,"abstract":"Introduction: The cardiotoxicity and subsequent Heart Failure (HF) induced by Doxorubicin (DOX) limit the clinical application of DOX. Valsartan (Val) is an angiotensin II receptor blocker that could attenuate the HF induced by DOX. However, the underlying mechanism of Val in this process is not fully understood.Methods: In this study, we explored the cardio-protective mechanism of Val against DOX-induced cardiotoxicity using label-free ubiquitin-proteomic analysis.Results: Results showed that 27 lysine-ubiquitination sites in 25 proteins were differentially expressed between DOX and DOX+Val treated groups. In addition, the levels of ubiquitin modification of the myosin family and Ankrd1 were upregulated post-Val. Val also in-creased ATP production and activated the Akt/mTOR pathway by regulating the sarcoplas-mic/endoplasmic reticulum calcium ATPase (SERCA2a) and cardiomyocyte calcium hemo-stasis.Conclusion: The results highlight the value of label-free ubiquitin-proteomic analysis in de-fining the molecular mechanism of Val against HF and may be helpful in the development of new therapeutic agents for HF via targeting molecules defined in this research.","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current cancer drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680096341637241231111922","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: The cardiotoxicity and subsequent Heart Failure (HF) induced by Doxorubicin (DOX) limit the clinical application of DOX. Valsartan (Val) is an angiotensin II receptor blocker that could attenuate the HF induced by DOX. However, the underlying mechanism of Val in this process is not fully understood.

Methods: In this study, we explored the cardio-protective mechanism of Val against DOX-induced cardiotoxicity using label-free ubiquitin-proteomic analysis.

Results: Results showed that 27 lysine-ubiquitination sites in 25 proteins were differentially expressed between DOX and DOX+Val treated groups. In addition, the levels of ubiquitin modification of the myosin family and Ankrd1 were upregulated post-Val. Val also in-creased ATP production and activated the Akt/mTOR pathway by regulating the sarcoplas-mic/endoplasmic reticulum calcium ATPase (SERCA2a) and cardiomyocyte calcium hemo-stasis.

Conclusion: The results highlight the value of label-free ubiquitin-proteomic analysis in de-fining the molecular mechanism of Val against HF and may be helpful in the development of new therapeutic agents for HF via targeting molecules defined in this research.

查看原文本刊更多论文

无标记泛素-蛋白质组学分析在确定缬沙坦抗阿霉素诱导心力衰竭保护机制中的价值。

多柔比星（DOX）引起的心脏毒性和随后的心力衰竭（HF）限制了DOX的临床应用。缬沙坦（Val）是一种血管紧张素II受体阻滞剂，可减弱DOX诱导的HF。然而，Val在这一过程中的潜在机制尚不完全清楚。方法：采用无标记泛素-蛋白质组学分析方法，探讨缬氨酸对dox诱导的心脏毒性的保护机制。结果：DOX与DOX+Val处理组25个蛋白中27个赖氨酸泛素化位点的表达存在差异。此外，肌球蛋白家族和Ankrd1的泛素修饰水平在val后上调。Val还通过调节肌浆/内质网钙ATP酶（SERCA2a）和心肌细胞钙血瘀，增加ATP的产生，激活Akt/mTOR通路。结论：该结果突出了无标记泛素-蛋白质组学分析在确定Val抗HF分子机制方面的价值，并可能有助于通过本研究确定的分子靶向开发新的HF治疗药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.