Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor.
Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor.
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DOI：
10.18632/aging.100396
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Tsuda L
中科院分区：
文献类型：
--
作者：
Xiang L;Nakamura Y;Lim YM;Yamasaki Y;Kurokawa-Nose Y;Maruyama W;Osawa T;Matsuura A;Motoyama N;Tsuda L
O型叉头结构域转录因子（FOXO）参与许多生物学过程，如衰老、氧化应激反应和生长调节。FOXO活性在细胞内受到严格控制。特别是，生长因子信号通路和氧化应激反应都可以刺激这种转录因子的核转位。在这里，我们表明，四氢姜黄素（THC），姜黄素代谢产物，调节氧化应激反应和老化通过FOXO。在NIH 3 T3细胞中，THC通过抑制蛋白激酶B（PKB）/Akt的磷酸化，诱导FOXO 4（转录因子FOXO家族成员）的核积聚。在黑腹果蝇中，THC减弱了氧化应激反应，这种作用在foxo突变背景中被阻断。在正常条件下，四氢大麻酚也延长了果蝇的寿命，而foxo或Sir 2活性的丧失消除了这种效应。基于这些结果，THC可能通过包括foxo和Sir 2的进化上保守的信号通路来调节衰老过程。
The O-type forkhead domain transcription factor (FOXO) is involved in many biological processes such as aging, the oxidative stress response, and growth regulation. FOXO activity is tightly controlled within cells. In particular, growth factor signaling pathways and the oxidative stress response can both stimulate nuclear translocation of this transcription factor. Here, we show that tetrahydrocurcumin (THC), a curcumin metabolite, regulates the oxidative stress response and aging via FOXO. In NIH3T3 cells, THC induced nuclear accumulation of FOXO4, a member of the FOXO family of transcription factors, by inhibiting phosphorylation of protein kinase B (PKB)/Akt. In Drosophila melanogaster, THC attenuated the oxidative stress response, an effect that was blocked in a foxo mutant background. THC also extended the life span of Drosophila under normal conditions, and loss of either foxo or Sir2 activity eliminated this effect. Based on these results, THC may regulate the aging process via an evolutionarily conserved signaling pathway that includes both foxo and Sir2.
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影响因子：
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作者：
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DOI：
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