EndophilinA2 protects against angiotensin II‐induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes
| Autor: | Ling‐Yun Zheng, Xin-Qiu-Yue Wang, Jian-Dong Luo, Hai-Qi Liu, Yun Liu, Huan-Jia Shen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Genetic Vectors Primary Cell Culture Cell Apoptosis Cardiomegaly Transfection Endocytosis Biochemistry Receptor Angiotensin Type 1 Adenoviridae Rats Sprague-Dawley 03 medical and health sciences Internal medicine medicine Animals Myocytes Cardiac RNA Small Interfering Receptor Molecular Biology Heat-Shock Proteins Chemistry Angiotensin II Endoplasmic reticulum Cell Biology Endoplasmic Reticulum Stress medicine.disease Rats Protein Transport 030104 developmental biology Endocrinology medicine.anatomical_structure Animals Newborn Gene Expression Regulation Heart failure cardiovascular system Signal transduction Acyltransferases hormones hormone substitutes and hormone antagonists Intracellular Signal Transduction |
| Zdroj: | Journal of Cellular Biochemistry. 119:8290-8303 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.26862 |
| Popis: | Cardiac hypertrophy is one of the major risk factors for chronic heart failure. The role of endophilinA2 (EndoA2) in clathrin-mediated endocytosis and clathrin-independent endocytosis is well documented. In the present study, we tested the hypothesis that EndoA2 protects against angiotensin II (Ang II)-induced cardiac hypertrophy by mediating intracellular angiotensin II type 1 receptor (AT1-R) trafficking in neonatal rat cardiomyocytes (NRCMs). Cardiac hypertrophy was evaluated by using cell surface area and quantitative RT-PCR (qPCR) analyses. For the first time, we found that EndoA2 attenuated cardiac hypertrophy and fibrosis induced by Ang II. Moreover, EndoA2 inhibited apoptosis induced by excessive endoplasmic reticulum stress (ERS), which accounted for the beneficial effects of EndoA2 on cardiac hypertrophy. We further revealed that there was an interaction between EndoA2 and AT1-R.The expression levels of EndoA2, which inhibits AT1-R transport from the cytoplasm to the membrane, and the interaction between EndoA2 and AT1-R were obviously decreased after Ang II treatment. Furthermore, Ang II inhibited the co-localization of AT1-R with GRP-78, which was reversed by EndoA2 overexpression. In conclusion, our results suggested that EndoA2 plays a role in protecting against cardiac hypertrophy induced by Ang II, possibly by inhibiting AT1-R transport from the cytoplasm to the membrane to suppress signal transduction. |
| Databáze: | OpenAIRE |
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