| Autor: |
Yu, Kang-Ying, Wang, Ya-Ping, Wang, Lin-Hui, Jian, Yang, Zhao, Xiao-Dong, Chen, Jing-Wei, Murao, Koji, Zhu, Wei, Dong, Liang, Wang, Guo-Qing, Zhang, Guo-Xing |
| Předmět: |
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| Zdroj: |
Basic Research in Cardiology; Jul2014, Vol. 109 Issue 4, p1-16, 16p |
| Abstrakt: |
Autophagy has emerged as a powerful process in the response to cellular injury. The present study was designed to investigate signal transduction pathways in angiotensin II (Ang II)-induced autophagy. Rat vascular smooth muscle cells (VSMCs) were stimulated with different doses of Ang II (10-10 mol/L) for different time periods (6-72 h). Incubation with Ang II increased the production of reactive oxygen species (ROS), increased the LC3-II to LC3-I ratio, increased beclin-1 expression, and decreased SQSTM1/p62 expression in a dose- and time-dependent manner. In addition, Ang II increased autophagosome formation. Increased ROS production induced by Ang II was inhibited by Ang II type 1 receptor (AT1) blockers (Olmesartan and Candesartan, ARB), a NADPH Oxidase inhibitor (apocynin), and mitochondrial K channels inhibitor (5-hydroxydecanoate, 5HD). Ang II (10 mol/L, 48 h)-induced increase in the LC3-II to LC3-I ratio, the formation of autophagosomes, expression of beclin-1 and decrease in the expression of SQSTM1/p62 were also inhibited by pretreatment with 3-methyladenine or bafilomycin A1 (inhibitors of autophagy), olmesartan and candesartan (in dose-dependent manners), apocynin, 5HD, and siRNA Atg5. Our results indicate that Ang II increases autophagy levels via activation of AT1 receptor and NADPH oxidase. Mitochondrial K channels also play an important role in Ang II-induced autophagy. Our results may provide a new strategy for treatment of cardiovascular diseases with Ang II. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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