Suppression of thioredoxin-1 induces premature senescence in normal human fibroblasts.
Suppression of thioredoxin-1 induces premature senescence in normal human fibroblasts.
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DOI：
10.1016/j.bbrc.2010.01.026
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发表时间：
2010-02
影响因子：
3.1
通讯作者：
Jennifer J Young;A. Patel;P. Rai
中科院分区：
文献类型：
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作者：
Jennifer J Young;A. Patel;P. Rai
硫氧还蛋白（TRX）是一种普遍存在的多功能巯基蛋白，其在维持细胞氧化还原稳态中起重要作用。硫氧还蛋白-1（TRX 1）是TRX的主要亚型，其水平已被证明与生物体寿命和年龄相关的组织退化相关。因此，我们研究了抑制TRX 1水平对细胞衰老的直接功能影响，这是一种与组织变性和衰老密切相关的现象。我们发现，通过shRNA抑制TRX 1的表达，通过上调p53/p21 Cip 1/Waf 1和p16 INK 4肿瘤抑制通路，迅速诱导年轻人皮肤成纤维细胞的早衰。此外，通过引入SV 40大T抗原来抑制这些途径可以防止TRX 1抑制诱导的过早衰老，但不能防止对氧化应激的敏感性。因此，我们的研究结果表明，TRX 1除了作为氧化还原保护蛋白的功能外，还具有抑制正常细胞衰老的作用。
Thioredoxin (TRX) is a ubiquitous multifunctional thiol protein that is critically involved in maintaining cellular redox homeostasis. Levels of thioredoxin-1 (TRX1), the major isoform of TRX, have been shown to correlate with organismal lifespan and age-associated tissue deterioration. Accordingly, we investigated the direct functional effects of suppressing TRX1 levels on cellular senescence, a phenomenon intimately linked with tissue degeneration and aging. Here we find that suppression of TRX1 expression via shRNA rapidly induces premature senescence in young human skin fibroblasts through upregulation of the p53/p21Cip1/Waf1and p16INK4atumor suppressor pathways. Moreover, inhibition of these pathways by introduction of SV40 Large T Antigen prevents TRX1 suppression-induced premature senescence but not susceptibility to oxidative stressors. Thus our results suggest that TRX1 has a role in suppressing senescence in normal cells in addition to its function as a redox-protective protein.