2014 Fiscal Year Final Research Report
The Ubiquitin E3 Ligase ITCH Interacts with Thioredoxin-Interacting Protein and Ameliorates Reactive Oxygen Species-Induced Cardiotoxicity
| Project/Area Number |
25860228
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | ユビキチン転移酵素Itch / 活性酸素種 / ユビキチン・プロテアソームシステム / TXNIP |
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| Outline of Final Research Achievements |
The ubiquitin E3 ligase ITCH is an enzyme that plays a pivotal role in posttranslational modification by ubiquitin proteasomal protein degradation. Thioredoxin-interacting protein (TXNIP) is a negative regulator of thioredoxin system, which is an endogenous reactive oxygen species (ROS) scavenger. We focused on the functional role of ITCH and its interaction with TXNIP to elucidate the mechanism of cardiotoxicity induced by ROS. Overexpression of ITCH increased proteasomal TXNIP degradation and augmented thioredoxin activity, leading to inhibition of ROS generation and subsequent cardiomyocyte apoptosis in ROS-induced cardiotoxicity. In transgenic mice with cardiac-specific overexpression of ITCH, cardiac dysfunction and remodeling were restored compared with wild-type mice after ROS-induced cardiotoxicity. We demonstrated that ITCH targets TXNIP for ubiquitin-proteasome degradation in cardiomyocytes and ameliorates ROS-induced cardiotoxicity through thioredoxin system.
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| Free Research Field |
細胞内シグナル伝達、ユビキチン・プロテアソームシステム
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