Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation
Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation
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DOI：
10.1002/mnfr.201500144
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发表时间：
2015-10-01
影响因子：
5.2
通讯作者：
Tsai, Kun-Ling
中科院分区：
文献类型：
--
作者：
Hung, Ching-Hsia;Chan, Shih-Hung;Tsai, Kun-Ling
范围：动脉粥样硬化被认为是心血管疾病的独立预测因子。越来越多的证据表明，槲皮素是一种有效的抗氧化剂和抗炎化合物。其对人内皮细胞氧化应激保护作用的分子机制尚不清楚。本研究旨在证实槲皮素通过激活sirtuin 1（SIRT 1）抑制氧化低密度脂蛋白（oxLDL）诱导的内皮细胞氧化损伤的假说，并探讨腺苷酸激活蛋白激酶（AMPK）的作用方法和结果：人脐静脉内皮细胞用oxLDL处理，槲皮素预处理或不预处理。我们发现槲皮素预处理增加SIRT 1 mRNA的表达。事实上，槲皮素可以保护oxLDL损伤的SIRT 1和AMPK活性，并减少oxLDL激活的NOX 2和NOX 4。然而，沉默SIRT 1和AMPK减弱了槲皮素对氧化损伤的保护功能。oxLDL可抑制AKT/内皮NO合成酶的表达，损伤线粒体功能，促进活性氧的形成，激活核因子-κ B（NF-κ B B）通路。槲皮素通过激活SIRT 1和调节AMPK/NADPH氧化酶/AKT/内皮NO合成酶信号通路抑制oxLDL诱导的内皮氧化损伤。
Scope: Atherosclerosis is believed to be an independent predictor of cardiovascular diseases. A growing body of evidence suggests that quercetin is a potent antioxidant and anti-inflammatory compound. The molecular mechanisms underlying its protective effects against oxidative stress in human endothelial cells remain unclear. This study was designed to confirm the hypothesis that quercetin inhibits oxidized LDL (oxLDL) induced endothelial oxidative damage by activating sirtuin 1 (SIRT1) and to explore the role of adenosine monophosphate activated protein kinase (AMPK), which is a negative regulator of Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) and free radicals.Methods and results: Human umbilical vein endothelial cells were treated with oxLDL with or without quercetin pretreatment. We found that quercetin pretreatment increased SIRT1 mRNA expression. In fact, quercetin protected against oxLDL-impaired SIRT1 and AMPK activities and reduced oxLDL-activated NOX2 and NOX4. However, silencing SIRT1 and AMPK diminished the protective function of quercetin against oxidative injuries. The results also indicated that oxLDL suppressed AKT/endothelial NO synthase, impaired mitochondrial dysfunction, and enhanced reactive oxygen species formation, activating the Nuclear Factor Kappa B (NF-kappa B) pathway.Conclusion: These results provide new insight regarding the possible molecular mechanisms of quercetin. Quercetin suppresses oxLDL-induced endothelial oxidative injuries by activating SIRT1 and modulating the AMPK/NADPH oxidase/AKT/endothelial NO synthase signaling pathway.