Functional analysis of Ubiquitin ligase Itch in doxorubicin-induced cardiomyopathy

泛素连接酶 Itch 在阿霉素诱导的心肌病中的功能分析

• 批准号: 22790684
• 负责人: TAKAHASHI Hiroki
• 金额: $ 2.16万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790684/
• 关键词: ドキソルビシン心筋症; ユビキチン転移酵素Itch; アポトーシス; Ubiquitination; ユビキチン転移酵素; Itch

In the present study, we focused on the interaction of ubiquitin E3 ligase Itch (a member of Ubiquitin-Proteasome system) and TXNIP to elucidate the mechanism for doxorubicin-induced cardiotoxicity. Knockdown of Itch attenuated doxorubicin-induced TXNIP degradation and subsequent increase in cleaved caspase-3. Furthermore, overexpression of Itch augmented doxorubicin-induced TXNIP degradation and resulted in reduction of cleaved caspase-3. These results suggest that Itch is one of potential target protein to prevent doxorubicin-induced cardiotoxicity.

本研究旨在探讨泛素-蛋白酶体系统中泛素E3连接酶Itch与TXNIP的相互作用，以阐明阿霉素心脏毒性的机制。Itch的敲除减弱了阿霉素诱导的TXNIP降解和随后裂解的caspase-3的增加。此外，过度表达Itch增强了阿霉素诱导的TXNIP降解，并导致切割的caspase-3减少。这些结果表明，Itch是预防阿霉素心脏毒性的潜在靶蛋白之一。