ole for Activating Transcription Factor 3 in Pressure Overload-induced Cardiac Dysfunction
| Autor: | Li-Chen Ma, 馬立貞 |
|---|---|
| Rok vydání: | 2011 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 99 Ventricular hypertrophy is mainly caused by sustained afterload which promotes cardiomyocytes apoptosis and necrosis and finally results in heart failure. The activating transcription factor 3 (ATF3) is a basic region-leucine zipper (bZip) transcription factor which belongs to the CREB/ATF family and can be induced in some kinds of stress. Previous studies indicated that ATF3 would be induced in response to the ROS stress after the treatment of ischemia/reperfusion in the heart. However, it is still a mystery what the role of ATF3 plays in pressure-overload heart failure. The aim of this study is to explore the molecular mechanisms how ATF3 protects heart from thoracic aortic banding (TAB)-induced cardiac dilatation in ATF3 knockout model. Our result showed that ATF3 can be induced in the nucleus of cardiacmyocyte of wild-type mice 3 days after TAB treatment. ATF3 knockout mice are also susceptible to cardiac dilatation 4 weeks after TAB treatment. In addition, several indicators of heart damage, including hypertrophy marker (β-MHC, ANP, and BNP), apoptosis level (TUNEL), activated casepae-3 and troponin I expression, were expressed highly in ATF3 knockout mice compared with wild-type mice. Then, we found the rescued expression of ATF3 by AVV-ATF3 delivery can improve the abnormal cardiac function in ATF3 knockout mice after TAB treatment. Molecular and biochemical analysis revealed that ATF3 can bind to the element of ATF/CRE on Beclin-1 promoter, and inhibited the luciferase expression driven by Beclin-1 promoter. Taken together, we proved that ATF3 can protect cardiomyocytes from over-autophagy death via inhibiting beclin-1 gene expression. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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