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Enhancing calmodulin binding to cardiac ryanodine receptor completely inhibits pressure-overload induced hypertrophic signaling.
Kohno, Michiaki; Kobayashi, Shigeki; Yamamoto, Takeshi; Yoshitomi, Ryosuke; Kajii, Toshiro; Fujii, Shohei; Nakamura, Yoshihide; Kato, Takayoshi; Uchinoumi, Hitoshi; Oda, Tetsuro; Okuda, Shinichi; Watanabe, Kenji; Mizukami, Yoichi; Yano, Masafumi.
Afiliación
  • Kohno M; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Kobayashi S; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Yamamoto T; Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, 755-8505, Japan.
  • Yoshitomi R; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Kajii T; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Fujii S; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Nakamura Y; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Kato T; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Uchinoumi H; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Oda T; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Okuda S; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
  • Watanabe K; Institute of Gene Research, Yamaguchi University Science Research Center, Yamaguchi, 755-8505, Japan.
  • Mizukami Y; Institute of Gene Research, Yamaguchi University Science Research Center, Yamaguchi, 755-8505, Japan.
  • Yano M; Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan. yanoma@yamaguchi-u.ac.jp.
Commun Biol ; 3(1): 714, 2020 11 26.
Article en En | MEDLINE | ID: mdl-33244105
Cardiac hypertrophy is a well-known major risk factor for poor prognosis in patients with cardiovascular diseases. Dysregulation of intracellular Ca2+ is involved in the pathogenesis of cardiac hypertrophy. However, the precise mechanism underlying cardiac hypertrophy remains elusive. Here, we investigate whether pressure-overload induced hypertrophy can be induced by destabilization of cardiac ryanodine receptor (RyR2) through calmodulin (CaM) dissociation and subsequent Ca2+ leakage, and whether it can be genetically rescued by enhancing the binding affinity of CaM to RyR2. In the very initial phase of pressure-overload induced cardiac hypertrophy, when cardiac contractile function is preserved, reactive oxygen species (ROS)-mediated RyR2 destabilization already occurs in association with relaxation dysfunction. Further, stabilizing RyR2 by enhancing the binding affinity of CaM to RyR2 completely inhibits hypertrophic signaling and improves survival. Our study uncovers a critical missing link between RyR2 destabilization and cardiac hypertrophy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calmodulina / Cardiomegalia / Canal Liberador de Calcio Receptor de Rianodina / Señalización del Calcio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Commun Biol Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calmodulina / Cardiomegalia / Canal Liberador de Calcio Receptor de Rianodina / Señalización del Calcio Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Commun Biol Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido