Functional analysis of Ubiquitin ligase Itch in doxorubicin-induced cardiomyopathy

• Project/Area Number: 22790684
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Yamagata University
• Principal Investigator: TAKAHASHI Hiroki 山形大学, 医学部, 助教 (90400548)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 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

Research Abstract

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.