Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells

被引:195
作者
Ikushima, M [1 ]
Rakugi, H [1 ]
Ishikawa, K [1 ]
Maekawa, Y [1 ]
Yamamoto, K [1 ]
Ohta, J [1 ]
Chihara, Y [1 ]
Kida, I [1 ]
Ogihara, T [1 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Geriatr Med, Suita, Osaka, Japan
关键词
Klotho; apoptosis; senescence; oxidative stress; endothelial cell;
D O I
10.1016/j.bbrc.2005.11.094
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Klotho-mutated mice manifest multiple age-related disorders that are observed in humans. A recent study suggested that Klotho protein might function as an anti-aging hormone in mammals. Because it has been reported that apoptosis and senescence in vascular endothelial cells are closely related to the progression of atherosclerosis, we investigated Klotho's ability to interfere with apoptosis and cellular senescence in human umbilical vascular endothelial cells (HUVEC). Klotho overexpression decreased H(2)O(2)-induced apoptosis in COS-I cells and Jurkat cells. Klotho protein also reduced H(2)O(2)- and etoposide-induced apoptosis in HUVEC. Caspase-3 and caspase-9 activity was lower in Klotho-treated HUVEC than in control cells. Senescence-associated beta-gal staining showed that Klotho protein interferes with H(2)O(2)-induced premature cellular senescence. The expression of p53 and p21 was lower in Klotho-treated cells. Our study suggests that Klotho acts as a humoral factor to reduce H(2)O(2)-induced apoptosis and cellular senescence in vascular cells. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:827 / 832
页数:6
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