2015 Fiscal Year Final Research Report
The HECT-Type Ubiquitin E3 Ligase ITCH Interacts with Thioredoxin-Interacting Protein and Ameliorates Reactive Oxygen Species-Induced Cardiotoxicity
| Project/Area Number |
26893025
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Cardiovascular medicine
|
|---|
| Research Institution | Yamagata University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-08-29 – 2016-03-31
|
| Keywords | 酸化ストレス / ユビキチン / ITCH |
|---|
| Outline of Final Research Achievements |
The HECT-Type 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. We focused on the functional role of ubiquitin E3 ligase ITCH and its interaction with TXNIP to elucidate the mechanism of cardiotoxicity induced by ROS. Protein interaction between TXNIP and ITCH was confirmed by immunoprecipitation assays. Overexpression of ITCH increased proteasomal TXNIP degradation and inhibited ROS generation, p38 MAPK, p53, and subsequent intrinsic pathway apoptosis in ROS-induced cardiotoxicity. We generated ITCH transgenic mouse. In ITCH-Tg mice, cardiac dysfunction and remodeling were restored compared with wild-type littermates after Dox injection and myocardial infarction surgery. ITCH targets TXNIP for ubiquitin-proteasome degradation and ameliorates ROS-induced cardiotoxicity through the thioredoxin system.
|
| Free Research Field |
心不全
|
