Central role of SIAH inhibition in DCC-dependent cardioprotection provoked by netrin-1/NO
Abstrak
Significance Therapies for myocardial infarction consequent to ischemia/reperfusion injury (I/R) have been lacking. The netrin-1 receptor deleted in colorectal cancer (DCC) mediates netrin-1–dependent cardioprotective signaling. It is anticipated that any means of augmenting DCC signaling may induce cardioprotection on its own and enhance netrin-1/NO–dependent cardioprotection. The present study identifies a novel mechanism by which NO upregulates DCC abundance. NO inhibits seven in absentia homolog (SIAH), an E3 ubiquitin ligase that suppresses DCC. Inhibition of SIAH by in vivo RNA interference markedly reduces infarct size to improve cardiac function that was determined by echocardiography. Combined with netrin-1 perfusion, it further potentiated netrin-1’s cardioprotective effect. SIAH may therefore serve as a novel therapeutic target for myocardial infarction, particularly those suffering from cardiac I/R injury.
Penulis (4)
Qiang Li
Ping Wang
Keqiang Ye
Hua Cai
Akses Cepat
- Tahun Terbit
- 2015
- Bahasa
- en
- Total Sitasi
- 34×
- Sumber Database
- CrossRef
- DOI
- 10.1073/pnas.1420695112
- Akses
- Open Access ✓