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Ampelopsin protects endothelial cells from hyperglycemia‐induced oxidative damage by inducing autophagy via the AMPK signaling pathway
Author(s) -
Liang Xinyu,
Zhang Ting,
Shi Linying,
Kang Chao,
Wan Jing,
Zhou Yong,
Zhu Jundong,
Mi Mantian
Publication year - 2015
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1248
Subject(s) - autophagy , ampk , chemistry , atg5 , downregulation and upregulation , microbiology and biotechnology , pi3k/akt/mtor pathway , endothelial stem cell , protein kinase a , signal transduction , pharmacology , apoptosis , kinase , biology , biochemistry , in vitro , gene
Diabetic angiopathy is a major diabetes‐specific complication that often begins with endothelial dysfunction induced by hyperglycemia; however, the pathological mechanisms of this progression remain unclear. Ampelopsin is a natural flavonol that has strong antioxidant activity, but little information is available regarding its antidiabetic effect. This study focused on the effect of ampelopsin on hyperglycemia‐induced oxidative damage and the underlying mechanism of this effect in human umbilical vein endothelial cells (HUVECs). We found that hyperglycemia impaired autophagy in HUVECs through the inhibition of AMP‐activated protein kinase (AMPK), which directly led to endothelial cell damage. Ampelopsin significantly attenuated the detrimental effect of hyperglycemia‐induced cell dysfunction in a concentration‐dependent manner in HUVECs. Ampelopsin significantly upregulated LC3‐II, Beclin1, and Atg5 protein levels but downregulated p62 protein levels in HUVECs. Transmission electron microscopy and confocal microscopy indicated that ampelopsin notably induced autophagosomes and LC3‐II dots, respectively. Additionally, the autophagy‐specific inhibitor 3‐MA, as well as Atg5 and Beclin1 siRNA pretreatment, markedly attenuated ampelopsin‐induced autophagy, which subsequently abolished the protective effect of ampelopsin against hyperglycemia in HUVECs. Moreover, ampelopsin also increased AMPK activity and inhibited mTOR (mammalian target of rapamycin) complex activation. Ampelopsin‐induced autophagy was attenuated by the AMPK antagonist compound C but strengthened by the AMPK agonist AICAR (5‐minoimidazole‐4‐carboxamide ribonucleotide). Furthermore, AMPK siRNA transfection eliminated ampelopsin's alleviation of cell injury induced by hyperglycemia. The protective effect of ampelopsin against hyperglycemia‐induced cell damage, which functions by targeting autophagy via AMPK activation, makes it a promising pharmacological treatment for type‐2 diabetes. © 2015 BioFactors, 41(6):463–475, 2015