Isoquercitrin Inhibits Hydrogen Peroxide-Induced Apoptosis of EA.hy926 Cells via the PI3K/Akt/GSK3β Signaling Pathway.
Isoquercitrin Inhibits Hydrogen Peroxide-Induced Apoptosis of EA.hy926 Cells via the PI3K/Akt/GSK3β Signaling Pathway.
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DOI：
10.3390/molecules21030356
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发表时间：
2016-03-21
期刊：
影响因子：
--
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Zhu M;Li J;Wang K;Hao X;Ge R;Li Q
氧化应激在内皮损伤和多种心血管疾病（包括动脉粥样硬化）的发病机制中起着关键作用。异槲皮素（槲皮素-3-葡萄糖苷）是一种广泛分布于植物中的类黄酮，具有抗过敏、抗病毒、抗炎、抗氧化等多种生物活性。本研究观察异槲皮苷对h2o2诱导的EA.hy926细胞凋亡的抑制作用。MTT实验表明，异槲皮苷能显著抑制h2o2诱导的EA.hy926细胞活力丧失。Hoechst33342/PI和Annexin V-FITC/PI双荧光染色显示异槲皮素抑制h2o2诱导的EA.hy926细胞凋亡。Western blotting结果显示，异槲皮苷可以抑制h2o2诱导的cleaved caspase-9和cleaved caspase-3表达的增加，同时增加抗凋亡蛋白Mcl-1的表达。此外，异槲皮素显著增加EA.hy926细胞中p-Akt和p-GSK3β的表达，并呈剂量依赖性。PI3K/Akt抑制剂LY294002可抑制异槲皮素诱导的GSK3β磷酸化和Mcl-1表达升高，提示异槲皮素对Mcl-1表达的调控可能与调节Akt活化有关。这些结果表明，异槲皮苷对h2o2诱导的EA.hy926细胞的抗凋亡作用可能与异槲皮苷对Akt/GSK3β信号通路的调控有关，异槲皮苷可用于临床干预内皮损伤相关心血管疾病的进展。
Oxidative stress plays a critical role in endothelial injury and the pathogenesis of diverse cardiovascular diseases, including atherosclerosis. Isoquercitrin (quercetin-3-glucoside), a flavonoid distributed widely in plants, exhibits many biological activities, including anti-allergic, anti-viral, anti-inflammatory, and anti-oxidative effects. In the present study, the inhibitory effect of isoquercitrin on H2O2-induced apoptosis of EA.hy926 cells was evaluated. MTT assays showed that isoquercitrin significantly inhibited H2O2-induced loss of viability in EA.hy926 cells. Hoechst33342/PI and Annexin V-FITC/PI fluorescent double staining indicated that isoquercitrin inhibited H2O2-induced apoptosis of EA.hy926 cells. Western blotting demonstrated that isoquercitrin prevented H2O2-induced increases in cleaved caspase-9 and cleaved caspase-3 expression, while increasing expression of anti-apoptotic protein Mcl-1. Additionally, isoquercitrin significantly increased the expression of p-Akt and p-GSK3β in a dose-dependent manner in EA.hy926 cells. LY294002, a PI3K/Akt inhibitor, inhibited isoquercitrin-induced GSK3β phosphorylation and increase of Mcl-1 expression, which indicated that regulation of isoquercitrin on Mcl-1 expression was likely related to the modulation of Akt activation. These results demonstrated that the anti-apoptotic effect of isoquercitrin on H2O2-induced EA.hy926 cells was likely associated with the regulation of isoquercitrin on Akt/GSK3β signaling pathway and that isoquercitrin could be used clinically to interfere with the progression of endothelial injury-associated cardiovascular disease.
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影响因子：
--
作者：
Badran M;Ayas N;Laher I
通讯作者：
Laher I
影响因子：
5.4
作者：
Gasparotto Junior, Arquimedes;Gasparotto, Francielly Mourao;Leite Kassuya, Candida Aparecida
通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
13.6
作者：
Barton, M;Vos, I;Lüscher, TF
通讯作者：
Lüscher, TF
影响因子：
8.8
作者：
Batista, Angela Giovana;Ferrari, Angelica Simoes;Marostica Junior, Mario Roberto
通讯作者：
Marostica Junior, Mario Roberto