期刊
MOLECULAR MEDICINE REPORTS
卷 4, 期 2, 页码 255-260出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2011.436
关键词
senescence; angiotensin II; telomere length; losartan
资金
- Major Basic Project of China (973) [2007CB507400]
Telomeres are DNA repeats at the ends of linear chromosomes in eukaryotic cells; they form cap-like specialized structures at chromosome ends to protect them from digestion and degradation. With each cell division, somatic cell telomeres progressively wear and shorten, leading to cell senescence. Various environmental factors, such as oxidative stress and in can accelerate telomere shortening. The renin angiotensin system seems to be the key mechanism involved in aging. Our previous studies demonstrated that treatment of human glomerular mesangial cells (GMCs) with angiotensin II (AngII.) caused cell senescence. It is important to understand whether AngII accelerates telomere shortening in GMCs and further promotes aging. Therefore, this study was designed to investigate the change in telomere length in AngII-induced GMC senescence and the role of the AngII receptor antagonist losartan in delaying this process. The cells were synchronized and divided into a normal control group, an AngII group (AngII, 10(-6) mol/l) and an AngII + losartan group (losartan, 10(-5) mol/l), and were then cultured for 72 If. The telomere lengths were analyzed by Southern blot analysis, cell morphology was monitored, the cell cycle and beta-galactosidase staining were determined, and the expression of P53 and P21 proteins was assessed by Western blotting. Compared with the control group, the AngII group exhibited a markedly reduced telomere length, cell cycle arrest, enhanced beta-galactosidase staining, and elevated expression of P53 and P21. The AngII + losartan group displayed longer telomere lengths, further reduced beta-galactosidase staining and decreased P53 and P21 expression compared to the AngII group. This study confirms that AngIl induces the shortening of telomere lengths, P53 and P21 expression, cell cycle arrest, and the resulting cell senescence in GMCs. In addition, losartan significantly reduced telomere shortening and cell senescence.
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