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Exogenous spermine attenuates rat diabetic cardiomyopathy via suppressing ROS-p53 mediated downregulation of calcium-sensitive receptor.
Wang, Yuehong; Chen, Junting; Li, Siwei; Zhang, Xinying; Guo, Zuoming; Hu, Jing; Shao, Xiaoting; Song, Ningyang; Zhao, Yajun; Li, Hongzhu; Yang, Guangdong; Xu, Changqing; Wei, Can.
Afiliação
  • Wang Y; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Chen J; Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.
  • Li S; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Zhang X; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Guo Z; Department of Hepatobiliary and Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
  • Hu J; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Shao X; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Song N; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Zhao Y; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Li H; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Yang G; Department of Chemistry and Biochemistry, Laurentian University, Sudbury, P3E 2C6, Canada.
  • Xu C; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China.
  • Wei C; Department of Pathophysiology, Harbin Medical University, Harbin, 150081, China. Electronic address: canwei528@163.com.
Redox Biol ; 32: 101514, 2020 05.
Article em En | MEDLINE | ID: mdl-32234613
ABSTRACT
Diabetic cardiomyopathy (DCM) is a severe complication of type 1 diabetic (T1D) patients, manifested as combined diastolic and systolic dysfunction. DCM is associated with impaired calcium homeostasis secondary to decreased calcium-sensitive receptor (CaSR) expression. Spermine, a direct agonist of CaSR, was found deficient in cardiomyocytes of T1D rats. However, the role of spermine in DCM was unclear. Here, we examined the cardioprotective effect of exogenous spermine on DCM in streptozotocin (STZ) induced-T1D rats and high-glucose (HG)-incubated neonatal rat cardiomyocytes. Exogenous spermine significantly attenuated cardiac dysfunction in T1D rats, characterized by improved echocardiography, less fibrosis, reduced myocardial endoplasmic reticulum (ER) stress and oxidative stress, and increased expression of myocardial membrane CaSR. In cultured neonatal rat cardiomyocytes, exogenous spermine attenuated myocardial injury induced by HG treatment, demonstrated by restored cellular glucose uptake capacity, reduced expression of apoptotic markers, lowered level of oxidative stress, ER stress and unfolded protein response, and upregulated cell membrane CaSR. Mechanistically, the cardioprotective effect of spermine appeared dependent upon effective elimination of reactive oxygen species (ROS) and up-regulation of CaSR expression by suppressing the Nrf2-ROS-p53-MuRF1 axis. Taken together, these results suggest that exogenous spermine protects against DCM in vivo and in vitro, partially via suppressing ROS and p53-mediated downregulation of cell membrane CaSR.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus / Cardiomiopatias Diabéticas Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: Redox Biol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus / Cardiomiopatias Diabéticas Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: Redox Biol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: China