High NaCl promotes cellular senescence
High NaCl promotes cellular senescence
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DOI：
10.4161/cc.6.24.5084
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发表时间：
2007-12-15
期刊：
影响因子：
4.3
通讯作者：
Burg, Maurice B.
中科院分区：
文献类型：
--
作者：
Dmitrieva, Natalia I.;Burg, Maurice B.
高水平的细胞外NaCl可以增加哺乳动物组织培养细胞、活体肾髓细胞、秀丽隐杆线虫和海洋无脊椎动物的DNA断裂数量。它还被证明可以增加肾细胞中的活性氧，导致蛋白质和DNA的氧化。细胞衰老是对这种损伤的常见反应。因此，在目前的研究中，我们寻找暴露于高NaCl的细胞衰老的迹象。我们发现(1)暴露于高NaCl环境下的HeLa细胞增殖速度逐渐下降至停滞，细胞表现出衰老的迹象，包括肥大和自身荧光增加。(2)通过衰老相关β -半乳糖苷酶活性（sa - β -gal）测量，高NaCl加速了小鼠原代胚胎成纤维细胞衰老的出现。(3)高NaCl浓度会延缓线虫的生长，显著降低线虫的寿命，并伴有运动能力下降、sa - β -gal阳性细胞数量增加等加速衰老的特征。(4)正常持续暴露于高NaCl环境下的小鼠肾髓细胞，其p16(INK4)（另一衰老指标）的表达比与外周血相同NaCl水平的肾皮质细胞更早。我们得出结论，高浓度NaCl加速细胞衰老，很可能是由它引起的DNA断裂和氧化损伤引起的。
High extracellular NaCl was previously shown to increase the number of DNA breaks in mammalian cells in tissue culture, renal medullary cells in vivo, C. elegans and marine invertebrates. It was also shown to increase reactive oxygen species in renal cells, resulting in oxidation of proteins and DNA. Cellular senescence is a common response to such damage. Therefore, in the present studies we looked for signs of senescence in cells exposed to high NaCl. We find that (1) the rate of proliferation of HeLa cells exposed to high NaCl decreases gradually to the point of arrest, and the cells display signs of senescence, including hypertrophy and increased auto fluorescence. (2) High NaCl accelerates the appearance of senescence in primary mouse embryonic fibroblasts, as measured by senescence-associated beta-galactosidase activity (SA-beta-gal). (3) High NaCl retards growth and markedly decreases the life span of C. elegans, accompanied by features of accelerated aging, such as decreased locomotion and increased number of SA-beta-gal positive cells. (4) Mouse renal medullary cells, which are normally continuously exposed to high NaCl, express increased p16(INK4) (another indicator of senescence) much earlier than do cells in the renal cortex, which has the same level of NaCl as peripheral blood. We conclude that high NaCl accelerates cellular senescence and aging, most likely secondary to the DNA breaks and oxidative damage that it causes.