Phenethyl Isothiocyanate, a Dual Activator of Transcription Factors NRF2 and HSF1.
Phenethyl Isothiocyanate, a Dual Activator of Transcription Factors NRF2 and HSF1.
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DOI：
10.1002/mnfr.201700908
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发表时间：
2018-09
影响因子：
5.2
通讯作者：
Dinkova-Kostova AT
中科院分区：
文献类型：
--
作者：
Dayalan Naidu S;Suzuki T;Yamamoto M;Fahey JW;Dinkova-Kostova AT
十字花科蔬菜富含硫代葡萄糖苷，是异硫氰酸酯（ITCs）的生物前体分子。十字花科蔬菜的消费和化学保护之间的关系已被广泛记录在流行病学研究。异硫氰酸苯乙酯（PEITC）作为其芥子油苷前体芥花甙存在于十字花科蔬菜豆瓣菜（Nasturtium officinale）中。PEITC具有多种生物学效应，包括激活细胞保护途径，例如由转录因子核因子红细胞2 p45相关因子2（NRF 2）和转录因子热休克因子1（HSF 1）介导的细胞保护途径，并可引起表观基因组的变化。然而，在高浓度下，PEITC导致活性氧的积累和细胞骨架的变化，从而导致细胞毒性。这些活性的基础是PEITC与其蛋白质靶标中的半胱氨酸残基的巯基反应性。这种化学反应性凸显了PEITC剂量对于实现靶向选择性的至关重要性，在未来临床试验的设计中应仔细考虑这一点。
Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45‐related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on‐target selectivity, which should be carefully considered in the design of future clinical trials.
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影响因子：
14.9
作者：
Chorley BN;Campbell MR;Wang X;Karaca M;Sambandan D;Bangura F;Xue P;Pi J;Kleeberger SR;Bell DA
通讯作者：
Bell DA
影响因子：
10.9
作者：
Cang S;Ma Y;Chiao JW;Liu D
通讯作者：
Liu D
影响因子：
9.8
作者：
Bravi, MC;Armiento, A;De Mattia, G
通讯作者：
De Mattia, G
影响因子：
3.8
作者：
DAXENBICHLER, ME;SPENCER, GF;POWELL, RG
通讯作者：
POWELL, RG
DOI：
10.1073/pnas.172398899
发表时间：
2002-09-03
影响因子：
11.1
作者：
Dinkova-Kostova, AT;Holtzclaw, WD;Talalay, P
通讯作者：
Talalay, P