Donepezil attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells through SIRT1 activation.

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Zhang T, Tian F, Wang J, Zhou S, Dong X, Guo K, Jing J, Zhou Y, Chen Y

Donepezil attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells through SIRT1 activation.

Cell Stress Chaperones. 2015 Sep;20(5):787-92. doi: 10.1007/s12192-015-0601-4. Epub 2015 Jul 21.

PubMed ID

26194321 [ View in PubMed

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Abstract

Cellular senescence of endothelial cells is a damage and stress response which induces pro-inflammatory, pro-atherosclerotic, and pro-thrombotic phenotypes. Donepezil is a drug used for the treatment of mild to moderate dementia of the Alzheimer's disease (AD). The aim of the present study was to investigate the attenuation of endothelial cell senescence by donepezil and to explore the mechanisms underlying the anti-aging effects of donepezil. Our results indicated that high glucose (HG) markedly decreased cell viability of human umbilical vein endothelial cells (HUVECs), and this phenomenon was reversed by treatment with donepezil. Importantly, our results displayed that the frequency of senescent (SA-ss-gal-positive) cells and the expression level of senescence genes (PAI-1 and p21) were significantly higher in the HG group compared with the normal glucose (NG) group, and these changes were blocked by treatment with donepezil. Also, our results showed that donepezil inhibits the generation of reactive oxygen species (ROS), which promotes cellular senescence. Pretreatment with nicotinamide (NAM), a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated with donepezil. Indeed, our results indicated that donepezil increased the SIRT1 enzyme activity. Therefore, these results show that donepezil delays cellular senescence that is promoted under HG condition via activation of SIRT1.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Donepezil	Interleukin-1 beta	Protein	Humans	Unknown	Inhibitor Inducer	Details