کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2533745 1559066 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh
چکیده انگلیسی

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 Gh expression and membrane translocation. Rosuvastatin inhibited Gh protein activity in cardiomyocytes by inhibiting basal and norepinephrine-stimulated mRNA transcription, protein expression and membrane translocation; however, norepinephrine-stimulated Gq 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. Gh protein is a novel target of statins in myocardial hypertrophy, and statin treatment may directly suppress cardiac hypertrophy through a large Gh protein-coupled pathway regardless of the regulation of small GTPases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 627, Issues 1–3, 10 February 2010, Pages 56–62
نویسندگان
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