Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh
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| Název: | Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of Gh |
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| Autoři: | Woochul Chang, Min Ji Cha, Hye Jung Kim, Namsik Chung, Byeong-Wook Song, Eun-Ju Choi, Yangsoo Jang, Soyeon Lim, Eui-Young Choi, Ki-Chul Hwang |
| Přispěvatelé: | 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 |
| Zdroj: | European Journal of Pharmacology. 627:56-62 |
| Informace o vydavateli: | Elsevier BV, 2010. |
| Rok vydání: | 2010 |
| Témata: | Myosin Light Chains/genetics, 0301 basic medicine, Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism, Intracellular Space/drug effects, Cardiomegaly/metabolism, Norepinephrine/pharmacology, Proto-Oncogenes/genetics, Intracellular Space, Down-Regulation/drug effects, Messenger/metabolism, Norepinephrine, Extracellular Signal-Regulated MAP Kinases/metabolism, Cardiac Myosins/metabolism, Myocytes, Cardiac, Rosuvastatin Calcium, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Cardiomyocytes, 0303 health sciences, Intracellular Space/metabolism, Pyrimidines/pharmacology, GTP-Binding Proteins/metabolism, 3. Good health, Protein Transport, Small Interfering/genetics, Cardiac/metabolism, G-proteins, Cardiomegaly/pathology, Calcium/metabolism, Myosin Light Chains, Down-Regulation, Cardiomegaly, Transfection, Rosuvastatin, 03 medical and health sciences, GTP-Binding Proteins, Cardiac Myosins/genetics, Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology, Proto-Oncogenes, Animals, RNA, Messenger, GTP-Binding Proteins/genetics, Myocytes, Cell Membrane/drug effects, Base Sequence, Cardiomegaly/chemically induced, Cell Membrane/metabolism, Cell Membrane, Hypertrophy, Protein Transport/drug effects, Sulfonamides/pharmacology, Rats, GTP-Binding Proteins/deficiency, Fluorobenzenes, Cardiac/drug effects, Pyrimidines, Fluorobenzenes/pharmacology, Myosin Light Chains/metabolism, RNA, Messenger/genetics, Calcium, Sprague-Dawley, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiac Myosins |
| Popis: | 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. |
| Druh dokumentu: | Article |
| Popis souboru: | 56~62 |
| Jazyk: | English |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2009.10.050 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/19883640 https://www.sciencedirect.com/science/article/pii/S0014299909009571 https://europepmc.org/article/MED/19883640 https://ir.ymlib.yonsei.ac.kr/handle/22282913/100556 https://yonsei.pure.elsevier.com/en/publications/rosuvastatin-inhibits-norepinephrine-induced-cardiac-hypertrophy- https://pubmed.ncbi.nlm.nih.gov/19883640/ |
| Rights: | Elsevier TDM CC BY NC ND |
| Přístupové číslo: | edsair.doi.dedup.....8b00e6ff376167e7e201a9131e04f1b3 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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. |
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| ISSN: | 00142999 |
| DOI: | 10.1016/j.ejphar.2009.10.050 |