Role of Calcineurin in Insulin-Like Growth Factor-1-Induced Hypertrophy of Cultured Adult Rat Ventricular Myocytes

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• The present study examined the role of calcineurin in insulin-like growth factor(IGF)-1-induced hypertrophy in primary cultures of adult rat ventricular myocytes(ARVM), prepared from the ventricles of 14-16-week-old male Sprague-Dawley rats. The effects of several humoral factors, including phenylephrine, angiotensin II, endothelin-1, IGF-1 and interleukin-6, on the morphology of ARVM were studied. Myocyte surface area was significantly increased by IGF-1(2, 268±571 to 3, 018±836μm^2, p<0.01), but not by other humoral factors. This hypertrophic effect of IGF-1 was blocked by genistein(tyrosine kinase inhibitor), PD98059(MEK inhibitor). These findings suggest that IGF-1 produces ARVM hypertrophy by a tyrosine kinase-MEK mediated pathway as has been reported in neonatal cardiomyocytes. IGF-1-mediated ARVM hypertrophy was also attenuated by cyclosporine A(calcineurin inhibitor), and staurosporine and chelerythrine(protein kinase C inhibitors). IGF-1 markedly increased calcineurin activity(8.7±1.2 to 98.0±54.3 pmol・h^<-1>・mg^<-1> p<0.01), and this activation was completely blocked by pre-treatment with cyclosporine A(8.5±11.4pmol・h^<-1>mg^<-1> p<0.01)and chelerythrine(2.3±2.7 pmol・h^<-1>・mg^<-1> p<0.01). It appears that IGF-1 activates calcineurin by a protein kinase C-dependent pathway. Increased mRNA expression of atrial natriuretic factor by IGF-1 was inhibited by cyclosporine A(p<0.01). The findings indicate that IGF-1 induces ARVM hypertrophy by protein kinase C and calcineurin-related mechanisms. The fact that elevated calcineurin activity and induced atrial natriuretic factor mRNA expression by IGF-1 were blocked by cyclosporine A further supports the hypothesis that calcineurin is critically involved in IGF-1-induced ARVM hypertrophy.

• 社団法人日本循環器学会の論文
• 2001-08-20

著者

• Takeishi Yasuchika

  First department of internal medicine, Fukushima Medical University

• Tomoike Hitonobu

  National Cardiovascular Center

• TAKAHASHI Hiroki

  First Department of Internal Medicine, Sapporo Medical University, School of Medicine

• Kubota Isao

  First Department of Internal Medicine Yamagata University School of Medicine

• Kubota Isao

  Department Of Cardiology Pulmonology And Nephrology Yamagata University School Of Medicine

• Takeishi Yasuchika

  First Department Of Internal Medicine Fukushima Medical University

• Miyashita Takehiko

  山形大学 医学部循環･呼吸･腎臓内科学

• TOMOIKE Hitonobu

  First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan

• Kato Shuichi

  Department Of Cardiology Pulmonology Nephrology Yamagata University School Of Medicine

• Katoh Shigehiko

  山形大学 医学部循環･呼吸･腎臓内科学

• Kawashima Sukehiko

  Department Of Cardiology Pulmonology And Nephrology Yamagata University School Of Medicine

• Miyamoto Takuya

  Department Of Cardiology Pulmonology And Nephrology Yamagata University School Of Medicine

• Miyamoto Takuya

  山形大学 医学部循環･呼吸･腎臓内科学

• MIYASHITA Takehiko

  First Department of Internal Medicine and Division of Radiology, Yamagata University School of Medic

• Kato Shuichi

  First Department of Internal Medicine, Yamagata University School of Medicine

• Takahashi Hiroki

  Department Of Cardiology Pulmonology And Nephrology Yamagata University School Of Medicine

• Tomoike Hitonobu

  First Department Of Internal Medicine Yamagata University School Of Medicine

• Tomoike Hitonobu

  First Department Of Internal Medicine Yamagata University Medical School

• Takahashi Hiroki

  First Department Of Internal Medicine Sapporo Medical University

• Kato Shuichi

  First Department Of Internal Medicine Yamagata University School Of Medicine

• Takahashi Hiroki

  First Department Of Internal Medicine Gunma University School Of Medicine

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