1. Resveratrol Upregulates Cardiac SDF-1 in Mice with Acute Myocardial Infarction through the Deacetylation of Cardiac p53.
- Author
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Hong W, Tatsuo S, Shou-Dong W, Qian Z, Jian-Feng H, Jue W, Chen J, Hai-Yan Q, and Yue-Jin Y
- Subjects
- Acetylation drug effects, Animals, Cell Hypoxia drug effects, Fibrosis, Gene Silencing drug effects, Heart Function Tests drug effects, Heart Ventricles drug effects, Heart Ventricles metabolism, Heart Ventricles pathology, Heart Ventricles physiopathology, Male, Mice, Mice, Inbred C57BL, Myocardial Infarction diagnostic imaging, Myocardial Infarction pathology, Myocardial Infarction physiopathology, Myocardium pathology, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Resveratrol, Sirtuin 1 metabolism, Ultrasonography, Chemokine CXCL12 metabolism, Myocardial Infarction metabolism, Myocardium metabolism, Stilbenes pharmacology, Tumor Suppressor Protein p53 metabolism, Up-Regulation drug effects
- Abstract
Aims: We previously demonstrated that resveratrol (RSV) administration causes cardiac stromal cell-derived factor (SDF)-1 upregulation and can enhance the mobilization of stem cells in mice with acute myocardial infarction (AMI). However, the upstream signal transduction involved in SDF-1 regulation in the setting of AMI and RSV administration remains unclear. Because RSV is a sirtuin 1 (SIRT1) activator and SIRT proteins act as deacetylases, we investigated the role of SIRT1 in SDF-1 upregulation and its subsequent effects., Methods and Results: In vitro experiments with H9C2 cardiomyocytes under hypoxia and serum-deprivation conditions showed that p53 acted upstream of SDF-1. RSV could not regulate SDF-1 effectively after SIRT1 silencing, indicating that it is dependent on SIRT1. Subsequently, male C57BL/6 mice were divided into four groups: 1) sham, 2) MI, 3) MI+RSV, and 4) MI+RSV plus nicotinamide, an inhibitor of the deacetylase activity of SIRT (MI+RSV+NAM). Compared with the sham mice, AMI caused a slight increase in the cardiac p53 level and resulted in significant SIRT1 downregulation and p53 acetylation or activation. Compared with the MI mice, MI+RSV administration improved the cardiac SDF-1 level and reversed the reduction of SIRT1 and the activation of p53. Furthermore, we observed less cardiac dysfunction in MI+RSV mice and determined that NAM abolished the effects of RSV., Conclusions: RSV enhances cardiac SDF-1 excretion after AMI partially through a SIRT1 normalization/p53 inactivation pathway.
- Published
- 2015
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