1-Deoxynojirimycin attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells

1-Deoxynojirimycin attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells
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DOI:
10.1016/j.exger.2014.03.025
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发表时间:
2014-07-01
影响因子:
3.9
通讯作者:
Tsuduki, Tsuyoshi
Tsuduki, Tsuyoshi
中科院分区:
医学2区
文献类型:
--
作者:
Shuang, E.;Kijima, Ryo;Tsuduki, Tsuyoshi

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以发现预防血管衰老的方法为目的,研究了来源于桑树的1-脱氧野尻霉素(DNJ)对内皮细胞衰老的影响。观察DNJ对高糖诱导的人脐静脉内皮细胞(HUVECs)衰老的影响。HUVECs分别在正常葡萄糖(5.6mmol/L,NG组)、正常葡萄糖+DNJ(10 μ mol/L,DNJ组)、高糖(30mmol/L,HG组)、高糖+DNJ(10 μ mol/L,HG + DNJ组)中培养,传代至衰老。HG组细胞增殖率明显低于NG组,DNJ可逆转HG组细胞增殖率下降的趋势。与NG组相比,HG组中衰老(SA-β-Gal阳性)细胞的频率和衰老基因(PAI-1和p21)的表达水平显著升高,并且这些变化被DNJ阻断。与NG组相比,HG组的单核细胞粘附、NF-kB活性和活性氧产生(所有这些都促进细胞衰老)显著增加,并且这些变化再次被DNJ阻断。因此,这些结果表明DNJ延迟了在高葡萄糖条件下促进的细胞衰老。(C)2014 Elsevier Inc. All rights reserved.
The influence of 1-deoxynojirimycin (DNJ) derived from mulberry on senescence of endothelial cells was examined with the goal of discovery of a method for prevention of senescence of blood vessels. The effect of DNJ on senescence of human umbilical vein endothelial cells (HUVECs) promoted under high glucose condition was determined. HUVECs were cultured in normal glucose (5.6 mmol/L, NG group), normal glucose plus DNJ (10 mu mol/L, DNJ group), high glucose (30 mmol/L, HG group), or high glucose plus DNJ (10 mu mol/L, HG + DNJ group) and passaged until they reached senescence. The proliferation rate was markedly decreased in the HG group compared with the NG group, and this phenomenon was reversed by DNJ. The frequency of senescent (SA-beta-Gal-positive) cells and the expression level of senescence genes (PAI-1 and p21) were significantly higher in the HG group compared with the NG group, and these changes were blocked by DNJ. Monocyte adhesion, NF-kB activity, and reactive oxygen species production, all of which promote cellular senescence, were significantly increased in the HG group compared with the NG group, and again these changes were blocked by DNJ. Therefore, these results show that DNJ delays cellular senescence that is promoted under high glucose condition. (C) 2014 Elsevier Inc. All rights reserved.