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通过NEDD4L介导的GPX4的Ubiquitination 恶化多克索鲁比诱导的心脏毒性

Jiaxing Ke¹, Lingjia Li¹, Shuling Chen¹

¹The Higher Educational Key Laboratory for Cardiovascular Disease of Fujian Province, Clinical Research Center for Metabolic Heart Disease of Fujian Province, Cardiovascular Department, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.

International journal of molecular sciences

|September 13, 2025

概括

doxorubicin 治疗会通过铁亡和亡引起心脏损伤. 这项研究表明,NEDD4L针对GPX4的降解,加剧了这种损伤,并确定NEDD4L是心脏毒性潜在的治疗点.

科学领域:

心脏病学心脏病学
分子生物学分子生物学
生物化学生物化学

背景情况:

多克索鲁比 (DOX) 是一种重要的化疗药物,但其使用受到多克索鲁比诱导的心脏毒性 (DIC) 的限制.
铁和亡是驱动DIC的关键机制.
在DIC中GPX4无处不在的作用尚不清楚.

研究的目的:

调查GPX4无化在多克索鲁比诱导心脏毒性的作用.
在DIC中识别负责GPX4ubiquitination的E3ubiquitin连酶.
探索NEDD4L作为DIC的潜在治疗点.

主要方法:

西方涂抹检测蛋白质无处不在和表达.
免疫沉以评估蛋白质与蛋白质相互作用.
细胞活力测定和TUNEL染色以评估心肌细胞死亡.
基因敲除使用siRNA来研究基因功能.

主要成果:

在DIC期间GPX4经历了无处不在的降解,加剧了心肌细胞中的铁和亡.
NEDD4L与GPX4相互作用,其表达由DOX上调.
通过减少GPX4的无处不在和降解,NEDD4L敲击减轻了DIC,铁和亡.
在DOX诱导的心肌细胞死亡中,GPX4是NEDD4L的关键下游标.

结论:

通过NEDD4L介导的GPX4无化和降解是多克索鲁比诱导心脏毒性的关键机制.
针对NEDD4L可能为预防和治疗DIC提供一种新的治疗策略.

关键词:

在GPX4中使用GPX4.在NEDD4L中,它是NEDD4L.心脏有毒性心脏有毒性德克索鲁比辛 (doxorubicin) 是一种药物.无处不在的化

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