Intermittent high glucose implements stress-induced senescence in human vascular endothelial cells: role of superoxide production by NADPH oxidase.
Intermittent high glucose implements stress-induced senescence in human vascular endothelial cells: role of superoxide production by NADPH oxidase.
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DOI：
10.1371/journal.pone.0123169
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kuzuya M
中科院分区：
文献类型：
--
作者：
Maeda M;Hayashi T;Mizuno N;Hattori Y;Kuzuya M
以餐后高血糖为特征的葡萄糖耐量受损，常发生在老年人中，是糖尿病的重要起始步骤，是动脉粥样硬化发展的独立危险因素。据报道，内皮细胞衰老先于动脉粥样硬化。我们报道了持续高葡萄糖刺激比高血压或血脂异常刺激更显著地引起内皮衰老。在本研究中，我们评估了波动的葡萄糖水平对人内皮细胞衰老的影响。持续高血糖增加衰老相关β-半乳糖苷酶（SA-β-gal）活性，这是一种广泛使用的细胞衰老标记物。有趣的是，在间歇性高葡萄糖中，这种作用以及p21和p16 INK 4a的增加更明显，这些蛋白与DNA损伤有关。然而，端粒酶没有被激活，端粒长度没有缩短，因此显示出应激诱导的衰老。而持续高糖则激活端粒酶活性，缩短端粒长度，提示复制性衰老。间歇性但非持续性高糖显著上调NADPH氧化酶组分p22 phox的表达，增加超氧化物。p22 phox的小干扰RNA破坏了间歇性高糖诱导的SA-β-gal活性的增加。结论：间歇性高糖比持续性高糖更能促进血管内皮细胞的衰老，其机制部分依赖于超氧化物的产生。
Impaired glucose tolerance characterized by postprandial hyperglycemia, which occurs frequently in elderly persons and represents an important preliminary step in diabetes mellitus, poses an independent risk factor for the development of atherosclerosis. Endothelial cellular senescence is reported to precede atherosclerosis. We reported that continuous high glucose stimulus causes endothelial senescence more markedly than hypertension or dyslipidemia stimulus. In the present study, we evaluated the effect of fluctuating glucose levels on human endothelial senescence. Constant high glucose increased senescence-associated-β-galactosidase(SA-β-gal) activity, a widely used marker for cellular senescence. Interestingly, in intermittent high glucose, this effect was more pronounced as well as increase of p21 and p16INK4a , senescence related proteins with DNA damage. However, telomerase was not activated and telomere length was not shortened, thus stress-induced senescence was shown. However, constant high glucose activated telomerase and shortened telomere length, which suggested replicative senescence. Intermittent but not constant high glucose strikingly up-regulated the expression of p22phox, an NADPH oxidase component, increasing superoxide. The small interfering RNA of p22phox undermined the increase in SA-β-gal activity induced by intermittent high glucose. Conclusively, intermittent high glucose can promote vascular endothelial senescence more than constant high glucose, which is in partially dependent on superoxide overproduction.
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影响因子：
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