Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6
Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6
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DOI：
10.1016/j.freeradbiomed.2016.04.013
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发表时间：
2016-07-01
影响因子：
7.4
通讯作者：
Balestrieri, Maria Luisa
中科院分区：
文献类型：
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作者：
D'Onofrio, Nunzia;Servillo, Luigi;Balestrieri, Maria Luisa
麦角硫因（Egt）是2-巯基-L-组氨酸的甜菜碱，是一种膳食抗氧化剂，通过不同于烷基硫醇的氧化还原机制预防许多疾病，包括心血管疾病（CVD）。在这里，实验的目的是评估潜在的机制Egt对高血压诱导的内皮细胞衰老的有益作用。为此，将细胞与递增浓度的Egt（0.01-1.00 mM）孵育12小时，然后与高葡萄糖（25 mM）孵育48小时。细胞评价表明，活力不受mM浓度的Egt和高葡萄糖的细胞毒性被阻止在0.5 mM Egt的最高功效。Egt的细胞保护作用是通过减少ROS的产生，细胞衰老，以及有趣的是，我们最近发现在Egt氧化途径过程中产生的甜菜碱（EH）的形成来实现的。值得注意的是，Egt的有益作用是通过上调沉默调节蛋白1（SIRT 1）和沉默调节蛋白6（SIRT 6）的表达以及下调p66 Shc和NF-κ B发挥的。SIRT 1活性抑制和SIRT 6基因沉默可阻断Egt对高糖诱导的内皮细胞衰老的保护作用。这些数据提供了Egt能够通过调节SIRT 1和SIRT 6信号传导来干扰与高血糖相关的内皮衰老的第一个证据，从而进一步加强了这两种组蛋白脱乙酰酶在2型糖尿病中已经评估的作用。(C)2016 Elsevier Inc. All rights reserved.
Ergothioneine (Egt), the betaine of 2-mercapto-L-histidine, is a dietary antioxidant protecting against many diseases, including cardiovascular disease (CVD), through a redox mechanism different from alkylthiols. Here, experiments were designed to evaluate the mechanisms underlying the beneficial effect of Egt against hyperglycaemia-induced senescence in endothelial cells. To this end, cells were incubated with increasing concentrations of Egt (0.01-1.00 mM) for 12 h followed by incubation for 48 h with high glucose (25 mM). Cell evaluation indicated that viability was not affected by mM concentrations of Egt and that the high-glucose cytotoxicity was prevented with the highest efficacy at 0.5 mM Egt. The cytoprotective effect of Egt was paralleled by reduced ROS production, cell senescence, and, interestingly, the formation of hercynine (EH), a betaine we recently found to be produced during the Egt oxidation pathway. Notably, the Egt beneficial effect was exerted through the upregulation of sirtuin 1 (SIRT1) and sirtuin 6 (SIRT6) expression and the downregulation of p66Shc and NF-kappa B. SIRT1 activity inhibition and SIRT6 gene silencing by small interfering RNA abolished the protective effect of Egt against the high glucose-induced endothelial senescence. These data provide the first evidence of the Egt ability to interfere with endothelial senescence linked to hyperglycaemia through the regulation of SIRT1 and SIRT6 signaling, thus further strengthening the already assessed role of these two histone deacetylases in type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.