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Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis 期刊论文

编号：

fccfbd18-a1b1-44f8-8086-c4f7ed5e1ff9
作者：

Gu, Junlian#^[1,2,3]Wang, Shudong(王树东)^[4]Guo, Hua^[3];Tan, Yi^[1,2,3];Liang, Yaqin^[5];Feng, Anyun^[1];Liu, Qiuju(刘秋菊)^[6]Damodaran, Chendil^[7];Zhang, Zhiguo(张志国)^[4]Keller, Bradley B.^[3,8];Zhang, Chi(张驰)*^[1,2]Cai, Lu^[1,2,3];
语种：

英文
期刊：

CELL DEATH & DISEASE ISSN：2041-4889 2018 年 9 卷 ; JAN 23
收录：
摘要：

Elevated tumor suppressor p53 expression has been associated with heart diseases, including the diabetic heart. However, its precise role in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. We hypothesized that the development of DCM is attributed to up-regulated p53-mediated both early cardiac cell death and persistent cell senescence, glycolytic and angiogenetic dysfunctions. The present study investigated the effect of p53 inhibition with its specific inhibitor pifithrin-alpha (PFT-alpha) on the pathogenesis of DCM and its associated mechanisms. Type 1 diabetes was induced with multiple low doses of streptozotocin. Both hyperglycemic and age-matched control mice were treated with and without PFT-alpha five times a week for 2 months and then sacrificed at 3 and 6 months post-diabetes. Treatment with PFT-alpha significantly prevented the progression of diabetes-induced cardiac remodeling and dysfunction (i.e., DCM). Mechanistically, the inhibition of p53 prevented the cardiac apoptosis during early-stage diabetes (0.5 month), attenuated diabetes-induced cell senescence (3 and 6 months), and improved both glycolytic and angiogenic defects by increasing hypoxia-induced factor (HIF)-1 alpha protein stability and upregulating HIF-1 alpha transcription of specific target genes at 3 and 6 months after diabetes. Therefore, the targeted inhibition of p53 in diabetic individuals may provide a novel approach for the prevention of DCM.
推荐引用方式
GB/T 7714：

Gu Junlian,Wang Shudong,Guo Hua, et al. Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis [J].CELL DEATH & DISEASE,2018,9.
APA：

Gu Junlian,Wang Shudong,Guo Hua,Tan Yi,&Cai Lu.(2018).Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis .CELL DEATH & DISEASE,9.
MLA：

Gu Junlian, et al. "Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis" .CELL DEATH & DISEASE 9(2018).
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