Angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of SOD2 and SIRT1.
Angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of SOD2 and SIRT1.
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DOI：
10.1371/journal.pone.0046459
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sato Y
中科院分区：
文献类型：
--
作者：
Miyashita H;Watanabe T;Hayashi H;Suzuki Y;Nakamura T;Ito S;Ono M;Hoshikawa Y;Okada Y;Kondo T;Sato Y
Vasohibin-1 (VASH1) 是一种内皮细胞 (EC) 产生的血管生成抑制剂。我们质疑VASH1除了抑制血管生成之外是否还发挥其他作用，在EC中敲低或过表达VASH1，并检查EC特性的变化。 VASH1的敲低会导致ECs过早衰老，并且这些ECs很容易被细胞应激杀死。相反，VASH1的过度表达使EC能够抵抗细胞应激引起的过早衰老和细胞死亡。 VASH1 的合成受到 HuR 介导的转录后调节的调节。我们试图定义潜在的机制。 VASH1 增加了（超氧化物歧化酶 2）SOD2 的表达，SOD2 是一种已知可以淬灭活性氧 (ROS) 的酶。同时，VASH1 增强了抗衰老蛋白 Sirtuin 1 (SIRT1) 的合成，从而提高了应激耐受性。百草枯在体内施用时会产生活性氧并导致器官损伤。更多 VASH1 (+/-) 小鼠因百草枯引起的急性肺损伤而死亡。气管内施用编码人 VASH1 的腺病毒载体可增强肺部 SOD2 和 SIRT1 的表达，并预防百草枯引起的急性肺损伤。因此，VASH1 是通过诱导 SOD2 和 SIRT1 提高 EC 应激耐受性的关键因素。
Vasohibin-1 (VASH1) is isolated as an endothelial cell (EC)-produced angiogenesis inhibitor. We questioned whether VASH1 plays any role besides angiogenesis inhibition, knocked-down or overexpressed VASH1 in ECs, and examined the changes of EC property. Knock-down of VASH1 induced premature senescence of ECs, and those ECs were easily killed by cellular stresses. In contrast, overexpression of VASH1 made ECs resistant to premature senescence and cell death caused by cellular stresses. The synthesis of VASH1 was regulated by HuR-mediated post-transcriptional regulation. We sought to define the underlying mechanism. VASH1 increased the expression of (superoxide dismutase 2) SOD2, an enzyme known to quench reactive oxygen species (ROS). Simultaneously, VASH1 augmented the synthesis of sirtuin 1 (SIRT1), an anti-aging protein, which improved stress tolerance. Paraquat generates ROS and causes organ damage when administered in vivo. More VASH1 (+/−) mice died due to acute lung injury caused by paraquat. Intratracheal administration of an adenovirus vector encoding human VASH1 augmented SOD2 and SIRT1 expression in the lungs and prevented acute lung injury caused by paraquat. Thus, VASH1 is a critical factor that improves the stress tolerance of ECs via the induction of SOD2 and SIRT1.
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影响因子：
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