Journal of cellular biochemistry, 2018-11, Vol.119 (10), p.8290-8303
2018
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- Autor(en) / Beteiligte
- Titel
- EndophilinA2 protects against angiotensin II‐induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes
- Ist Teil von
- Journal of cellular biochemistry, 2018-11, Vol.119 (10), p.8290-8303
- Ort / Verlag
- United States: Wiley Subscription Services, Inc
- Erscheinungsjahr
- 2018
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- 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. We identified EndoA2 as a novel molecule that regulates Ang II‐induced cardiac hypertrophy in NRCMs by mediating AT1‐R intracellular trafficking.These effects were at least partly regulated by AT1‐R trafficking between the cytoplasm and the surface membrane.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0730-2312eISSN: 1097-4644DOI: 10.1002/jcb.26862Titel-ID: cdi_proquest_journals_2118801409
- Format
- –
- Schlagworte
- Acyltransferases - antagonists & inhibitors, Acyltransferases - genetics, Acyltransferases - metabolism, Adenoviridae - genetics, Adenoviridae - metabolism, Angiotensin, Angiotensin II, Angiotensin II - genetics, Angiotensin II - metabolism, Angiotensin II - pharmacology, angiotensin II type 1 receptor trafficking, Animals, Animals, Newborn, Apoptosis, Apoptosis - genetics, cardiac hypertrophy, Cardiomegaly - chemically induced, Cardiomegaly - genetics, Cardiomegaly - physiopathology, Cardiomegaly - prevention & control, Cardiomyocytes, Cell surface, Clathrin, Cytoplasm, Endocytosis, endophilinA2, Endoplasmic reticulum, Endoplasmic Reticulum Stress - genetics, Fibrosis, Gene Expression Regulation, Genetic Vectors - chemistry, Genetic Vectors - metabolism, Heart, Heart diseases, Heat-Shock Proteins - genetics, Heat-Shock Proteins - metabolism, Hypertrophy, Localization, Myocytes, Cardiac - cytology, Myocytes, Cardiac - drug effects, Myocytes, Cardiac - metabolism, neonatal rat cardiomyocytes, Neonates, Primary Cell Culture, Protein Transport, Rats, Rats, Sprague-Dawley, Receptor, Angiotensin, Type 1 - genetics, Receptor, Angiotensin, Type 1 - metabolism, Risk analysis, Risk factors, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism, Signal Transduction, Transfection, Transport