Stachydrine Ameliorates High-Glucose Induced Endothelial Cell Senescence and SIRT1 Downregulation
Stachydrine Ameliorates High-Glucose Induced Endothelial Cell Senescence and SIRT1 Downregulation
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DOI：
10.1002/jcb.24598
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发表时间：
2013-11-01
影响因子：
4
通讯作者：
Balestrieri, Maria Luisa
中科院分区：
文献类型：
--
作者：
Servillo, Luigi;D'Onofrio, Nunzia;Balestrieri, Maria Luisa
高血糖是糖尿病的一个特征性特征，它通过加速内皮细胞（EC）衰老和限制这些细胞的增殖潜能而诱发内皮功能障碍和血管并发症。在这里，我们的目的是研究水水碱（一种脯氨酸甜菜碱，存在于柑橘属水果的果汁中）对高糖刺激下EC的影响及其潜在机制。采用不同时间高糖（30mM）处理细胞，建立EC衰老模型。剂量依赖性（0.001-1mM）的细胞活力评估显示，水苏水仙碱在72h内对细胞增殖没有影响，并且有类似的趋势。值得注意的是，水苏水仙碱（0.1mM）显著减弱高糖诱导的EC生长停滞和衰老。事实上，与高糖和水水碱共处理48h，使EC在G(0)/G(1)细胞周期阶段的百分比接近控制值，并显著减少细胞衰老。Western blot分析和共聚焦激光扫描显微镜显示，水苏水仙碱还阻断了高糖诱导的p16（INK4A）上调和SIRT1表达和酶活性下调。综上所述，本文的研究结果首次证明了水水碱（一种富含柑橘类果汁的天然化合物）可以抑制高糖对EC的有害影响，并通过调节SIRT1途径发挥作用。这些结果可能为确定水水碱是预防心血管疾病的健康饮食模式的重要组成部分开辟了新的前景。j .细胞。中国生物医学工程学报，2013,31(2):444 - 444。(c) 2013 Wiley Periodicals, Inc.；
Hyperglycaemia, a characteristic feature of diabetes mellitus, induces endothelial dysfunction and vascular complications by accelerating endothelial cell (EC) senescence and limiting the proliferative potential of these cells. Here we aimed to investigate the effect of stachydrine, a proline betaine present in considerable quantities in juices from fruits of the Citrus genus, on EC under high-glucose stimulation, and its underlying mechanism. The senescence model of EC was set up by treating cells with high-glucose (30mM) for different times. Dose-dependent (0.001-1mM) evaluation of cell viability revealed that stachydrine does not affect cell proliferation with a similar trend up to 72h. Noticeable, stachydrine (0.1mM) significantly attenuated the high-glucose induced EC growth arrest and senescence. Indeed, co-treatment with high-glucose and stachydrine for 48h kept the percentage of EC in the G(0)/G(1) cell cycle phase near to control values and significantly reduced cell senescence. Western blot analysis and confocal-laser scanning microscopy revealed that stachydrine also blocked the high-glucose induced upregulation of p16(INK4A) and downregulation of SIRT1 expression and enzyme activity. Taken together, results here presented are the first evidence that stachydrine, a naturally occurring compound abundant in citrus fruit juices, inhibits the deleterious effect of high-glucose on EC and acts through the modulation of SIRT1 pathway. These results may open new prospective in the identification of stachydrine as an important component of healthier eating patterns in prevention of cardiovascular diseases. J. Cell. Biochem. 114: 2522-2530, 2013. (c) 2013 Wiley Periodicals, Inc.