Mitochondrial KATP channel involvement in angiotensin II-induced autophagy in vascular smooth muscle cells
| Autor: | Jing-Wei Chen, Guo-Qing Wang, Ya-Ping Wang, Guo-Xing Zhang, Wei Zhu, Xiao-Dong Zhao, Lin-Hui Wang, Yang Jian, Kang-Ying Yu, Liang Dong, Koji Murao |
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| Jazyk: | angličtina |
| Předmět: |
Male
Vascular smooth muscle Potassium Channels Time Factors Physiology Muscle Smooth Vascular Autophagy-Related Protein 5 chemistry.chemical_compound Sequestosome-1 Protein Enzyme Inhibitors Cells Cultured Heat-Shock Proteins NADPH oxidase Angiotensin II Original Contribution cardiovascular system Beclin-1 RNA Interference Cardiology and Cardiovascular Medicine Microtubule-Associated Proteins hormones hormone substitutes and hormone antagonists medicine.drug Signal Transduction medicine.medical_specialty ATG5 Myocytes Smooth Muscle Biology Transfection Angiotensin II (Ang II) Receptor Angiotensin Type 1 Internal medicine Physiology (medical) medicine Autophagy Potassium Channel Blockers Animals Mitochondrial ATP-sensitive potassium channels Angiotensin II receptor type 1 Dose-Response Relationship Drug NADPH Oxidases Proteins Mitochondria Muscle Rats Candesartan Endocrinology chemistry LC3-II Apocynin biology.protein Apoptosis Regulatory Proteins Reactive Oxygen Species Angiotensin II Type 1 Receptor Blockers |
| Zdroj: | Basic Research in Cardiology |
| ISSN: | 0300-8428 |
| DOI: | 10.1007/s00395-014-0416-y |
| Popis: | 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(-9)-10(-5) 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 KATP channels inhibitor (5-hydroxydecanoate, 5HD). Ang II (10(-7) 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 KATP 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. |
| Databáze: | OpenAIRE |
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