Major differences among chemopreventive organoselenocompounds in the sustained elevation of cytoprotective genes.

Major differences among chemopreventive organoselenocompounds in the sustained elevation of cytoprotective genes.
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化学预防性有机硒化合物之间的主要差异在于细胞保护基因的持续升高。

DOI:
10.1002/jbt.21427
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发表时间:
2012
影响因子:
3.6
通讯作者:
Moos,PhilipJ
Moos,PhilipJ
中科院分区:
医学4区
文献类型:
--
作者:
Poerschke,RobynL;Franklin,MichaelR;Bild,AndreaH;Moos,PhilipJ

文献摘要

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细胞保护酶通过核红细胞2 p45相关因子2 (Nrf2) -Kelch样ECH相关蛋白1/抗氧化反应元件途径升高已被证实可预防癌症。本研究比较了有机硒化合物和萝卜硫素(SF)对肺细胞氧化还原损伤和持续细胞保护酶升高的影响。SF在2 h时引起活性氧(ROS)升高和谷胱甘肽(GSH)下降;Nrf2在4 h时的核积累;GSH在24小时内反弹并升高NAD(P)H醌氧化还原酶(NQO1)、硫氧还蛋白还原酶(TR1)和谷氨酸-半胱氨酸连接酶(GCL)。硒半胱氨酸(SECY)在24小时内引起了类似的反应,尽管较早的时间点变化较小。2‐环己基硒化唑烷‐4‐羧酸的作用与SECY相似,但Nrf2的变化更大,GSH、GCL、TR1和NQO1的24小时增幅最大。硒代蛋氨酸引起了类似的ROS的急性升高,但GSH的消耗较小,核Nrf2在4小时内没有增加,TR1和NQO1在24小时内只有轻微升高,GCL升高不足以升高GSH。©2012 Wiley期刊公司中国生物医学工程学报,2012;请登录wileyonlinelibrary.com在线阅读本文。DOI 10.1002 / jbt.21417
Cytoprotective enzyme elevation through the nuclear erythroid 2 p45‐related factor 2 (Nrf2)–Kelch‐like ECH‐associated protein 1/antioxidant response element pathway has been promulgated for cancer prevention. This study compares the redox insult and sustained cytoprotective enzyme elevation by organoselenocompounds and sulforaphane (SF) in lung cells. SF elicited a rise in reactive oxygen species (ROS) and drop in glutathione (GSH) at 2 h; nuclear accumulation of Nrf2 at 4 h; and a GSH rebound and elevation in NAD(P)H quinone oxidoreductase (NQO1), thioredoxin reductase (TR1), and glutamate–cysteine ligase (GCL) at 24 h. Selenocystine (SECY) elicited a similar 24 h response, despite lesser earlier time‐point changes. 2‐Cyclohexylselenazolidine‐4‐carboxylic acid effects were similar to SECY's but with a larger Nrf2 change and the largest 24 h increase in GSH, GCL, TR1, and NQO1 of any compound investigated. Selenomethionine elicited a similar acute rise in ROS, but lesser depletion of GSH, no 4 h increase in nuclear Nrf2, only minor 24 h elevations in TR1 and NQO1, and a GCL elevation insufficient to elevate GSH. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:344–353, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21417