ReferenceID 6236
Exogenous spermine attenuates rat diabetic cardiomyopathy via suppressing ROS-p53 mediated downregulation of calcium-sensitive receptor
Redox Biol
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 decrea
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Record Fields
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- Reference Id
- 6236
- Evidence Id
- 22826
- Core Evidence Id
- 22826
- Source Reference Id
- 5752
- Herb2 Reference Id
- HBREF006549
- Subject Paper Key
- HBIN044494_32234613
- Pubmed Id
- 32234613
- Doi
- 10.1016/j.redox.2020.101514
- Paper Title
- Exogenous spermine attenuates rat diabetic cardiomyopathy via suppressing ROS-p53 mediated downregulation of calcium-sensitive receptor
- Paper 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.
- Journal
- Redox Biol
- Publish Year
- 2020
- Experiment Subject
- rat; patient; cultured neonatal rat cardiomyocytes
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Diabetic Cardiomyopathy; Diastolic And Systolic Dysfunction; Cardiac Dysfunction; Type 1 Diabetic; Fibrosis
- Paper Title Cn
- Paper Title En
- Exogenous spermine attenuates rat diabetic cardiomyopathy via suppressing ROS-p53 mediated downregulation of calcium-sensitive receptor
- Bilingual Status
- semi_complete