Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells
Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells
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DOI：
10.1016/j.bbrc.2005.11.094
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发表时间：
2006-01-20
影响因子：
3.1
通讯作者：
Ogihara, T
中科院分区：
文献类型：
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作者：
Ikushima, M;Rakugi, H;Ogihara, T
Klotho突变的小鼠表现出在人类中观察到的多种与年龄相关的疾病。最近的一项研究表明，Klotho蛋白可能在哺乳动物中起着抗衰老激素的作用。由于已有报道血管内皮细胞的凋亡和衰老与动脉粥样硬化的进展密切相关，我们研究了Klotho对人脐静脉内皮细胞（HUVEC）凋亡和细胞衰老的干扰能力。Klotho过表达可降低COS-I细胞和Jurkat细胞中H（2）O（2）诱导的凋亡。Klotho蛋白还能减少H2 O2和依托泊苷诱导的HUVEC凋亡。Caspase-3和Caspase-9活性在Klotho处理的HUVEC中低于对照细胞。衰老相关的β-gal染色显示Klotho蛋白干扰H（2）O（2）诱导的细胞早衰。Klotho处理组p53和p21表达较对照组低。我们的研究表明Klotho作为一种体液因子，可以减少H（2）O（2）诱导的血管细胞凋亡和细胞衰老。(c)2005年爱思唯尔公司All rights reserved.
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.