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The RalGAPα1-RalA signal module protects cardiac function through regulating calcium homeostasis.
Zhu, Sangsang; Quan, Chao; Wang, Ruizhen; Liang, Derong; Su, Shu; Rong, Ping; Zhou, Kun; Yang, Xinyu; Chen, Qiaoli; Li, Min; Du, Qian; Zhang, Jingzi; Fang, Lei; Wang, Hong-Yu; Chen, Shuai.
Afiliação
  • Zhu S; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Quan C; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Wang R; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Liang D; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Su S; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Rong P; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Zhou K; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Yang X; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Chen Q; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Li M; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Du Q; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China.
  • Zhang J; School of Medicine, Nanjing University, Nanjing, China.
  • Fang L; School of Medicine, Nanjing University, Nanjing, China.
  • Wang HY; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China. wanghy
  • Chen S; State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, Nanjing University, Nanjing, China. schen6
Nat Commun ; 13(1): 4278, 2022 07 25.
Article em En | MEDLINE | ID: mdl-35879328
Sarcoplasmic/endoplasmic reticulum calcium ATPase SERCA2 mediates calcium re-uptake from the cytosol into sarcoplasmic reticulum, and its dysfunction is a hallmark of heart failure. Multiple factors have been identified to modulate SERCA2 activity, however, its regulation is still not fully understood. Here we identify a Ral-GTPase activating protein RalGAPα1 as a critical regulator of SERCA2 in cardiomyocytes through its downstream target RalA. RalGAPα1 is induced by pressure overload, and its deficiency causes cardiac dysfunction and exacerbates pressure overload-induced heart failure. Mechanistically, RalGAPα1 regulates SERCA2 through direct interaction and its target RalA. Deletion of RalGAPα1 decreases SERCA2 activity and prolongs calcium re-uptake into sarcoplasmic reticulum. GDP-bound RalA, but not GTP-bound RalA, binds to SERCA2 and activates the pump for sarcoplasmic reticulum calcium re-uptake. Overexpression of a GDP-bound RalAS28N mutant in the heart preserves cardiac function in a mouse model of heart failure. Our findings have therapeutic implications for treatment of heart failure.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cálcio / Insuficiência Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cálcio / Insuficiência Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article