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从蛋白质质量控制角度探索蒽环类药物诱导的心脏毒性

Exploring Anthracycline-Induced Cardiotoxicity from the Perspective of Protein Quality Control.

作者信息

Li Shanshan, Niu Weihua, Wang Chunyan, Zhao Jie, Zhang Na, Yin Yue, Jia Mei, Cui Liyan

机构信息

Department of Laboratory Medicine, Peking University Third Hospital, 100191 Beijing, China.

Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital, 100191 Beijing, China.

出版信息

Rev Cardiovasc Med. 2024 Jun 13;25(6):213. doi: 10.31083/j.rcm2506213. eCollection 2024 Jun.

Abstract

Anthracyclines are effective anticancer drugs; however, their use is restricted because of their dose-dependent, time-dependent and irreversible myocardial toxicity. The mechanism of anthracycline cardiotoxicity has been widely studied but remains unclear. Protein quality control is crucial to the stability of the intracellular environment and, ultimately, to the heart because cardiomyocytes are terminally differentiated. Two evolutionarily conserved mechanisms, autophagy, and the ubiquitin-proteasome system, synergistically degrade misfolded proteins and remove defective organelles. Recent studies demonstrated the importance of these mechanisms. Further studies will reveal the detailed metabolic pathway and metabolic control of the protein quality control mechanism integrated into anthracycline-induced cardiotoxicity. This review provides theoretical support for clinicians in the application and management of anthracyclines.

摘要

蒽环类药物是有效的抗癌药物;然而,由于其剂量依赖性、时间依赖性和不可逆的心肌毒性,其应用受到限制。蒽环类药物心脏毒性的机制已得到广泛研究,但仍不清楚。蛋白质质量控制对于细胞内环境的稳定性至关重要,最终对心脏也至关重要,因为心肌细胞是终末分化的。自噬和泛素 - 蛋白酶体系统这两种进化上保守的机制协同降解错误折叠的蛋白质并清除有缺陷的细胞器。最近的研究证明了这些机制的重要性。进一步的研究将揭示整合到蒽环类药物诱导的心脏毒性中的蛋白质质量控制机制的详细代谢途径和代谢控制。本综述为临床医生在蒽环类药物的应用和管理方面提供了理论支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4053/11270093/284a642d7b7b/2153-8174-25-6-213-g1.jpg

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