دورية أكاديمية
Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh
العنوان: | Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh |
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المساهمون: | Eui-Young Choi, Woochul Chang, Soyeon Lim, Byeong-Wook Song, Min-Ji Cha, Hye-Jung Kim, Eunju Choi, Yangsoo Jang, Namsik Chung, Ki-Chul Hwang, Choi, Eui Young, Hwang, Ki Chul, Jang, Yang Soo, Chung, Nam Sik |
سنة النشر: | 2010 |
مصطلحات موضوعية: | Animals, Base Sequence, Calcium/metabolism, Cardiac Myosins/genetics, Cardiac Myosins/metabolism, Cardiomegaly/chemically induced, Cardiomegaly/metabolism, Cardiomegaly/pathology, Cell Membrane/drug effects, Cell Membrane/metabolism, Down-Regulation/drug effects, Extracellular Signal-Regulated MAP Kinases/metabolism, Fluorobenzenes/pharmacology, GTP-Binding Proteins/deficiency, GTP-Binding Proteins/genetics, GTP-Binding Proteins/metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology, Intracellular Space/drug effects, Intracellular Space/metabolism, Myocytes, Cardiac/drug effects, Cardiac/metabolism, Myosin Light Chains/genetics, Myosin Light Chains/metabolism, Norepinephrine/pharmacology, Protein Transport/drug effects, Proto-Oncogenes/genetics, Pyrimidines/pharmacology, RNA, Messenger/genetics |
الوصف: | Statins have recently been shown to produce anti-cardiac hypertrophic effects via the regulation of small GTPases. However, the effects of statins on G protein-mediated cardiac hypertrophy, which is the main pathway of cardiac hypertrophy, have not yet been studied. We sought to evaluate whether statin treatment directly suppresses cardiac hypertrophy through a large G protein-coupled pathway regardless of the regulation of small GTPases. Using neonatal rat cardiomyocytes, we evaluated norepinephrine-induced cardiac hypertrophy for suppressibility of rosuvastatin and the pathways involved by analyzing total protein/DNA content, cell surface area, immunoblotting and RT-PCR for the signal transduction molecule. In a concentration-dependent manner, rosuvastatin inhibited total protein synthesis and downregulated basal and norepinephrine-induced expressions of myosin light chain2 and the c-fos proto-oncogene in cardiomyocytes. Treatment with norepinephrine induced cardiac hypertrophy accompanied by G(h) expression and membrane translocation. Rosuvastatin inhibited G(h) protein activity in cardiomyocytes by inhibiting basal and norepinephrine-stimulated mRNA transcription, protein expression and membrane translocation; however, norepinephrine-stimulated G(q) protein expression was not inhibited. In addition, the norepinephrine-stimulated protein kinase C (PKC)-mitogen-activated protein kinase (MEK 1,2)-extracellular signal-regulated kinases (ERKs) signaling cascade was inhibited by pretreatment with rosuvastatin. Rosuvastatin treatment also helped maintain expression levels of SERCA2a and intracellular calcium concentration. G(h) protein is a novel target of statins in myocardial hypertrophy, and statin treatment may directly suppress cardiac hypertrophy through a large G(h) protein-coupled pathway regardless of the regulation of small GTPases ; open |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | 56~62 |
اللغة: | unknown |
ردمك: | 978-0-01-429990-4 0-01-429990-9 |
تدمد: | 0014-2999 1879-0712 |
العلاقة: | EUROPEAN JOURNAL OF PHARMACOLOGY; J00842; OAK-2010-00156; https://ir.ymlib.yonsei.ac.kr/handle/22282913/100556Test; http://www.sciencedirect.com/science/article/pii/S0014299909009571Test; T201000166; EUROPEAN JOURNAL OF PHARMACOLOGY, Vol.627(1-3) : 56-62, 2010 |
DOI: | 10.1016/j.ejphar.2009.10.050 |
الإتاحة: | https://doi.org/10.1016/j.ejphar.2009.10.050Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/100556Test http://www.sciencedirect.com/science/article/pii/S0014299909009571Test |
حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ |
رقم الانضمام: | edsbas.6A4ABEB3 |
قاعدة البيانات: | BASE |
ردمك: | 9780014299904 0014299909 |
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تدمد: | 00142999 18790712 |
DOI: | 10.1016/j.ejphar.2009.10.050 |