Hydrogen peroxide is a second messenger in phase 2 enzyme induction by cancer chemopreventive dithiolethiones.
Hydrogen peroxide is a second messenger in phase 2 enzyme induction by cancer chemopreventive dithiolethiones.
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DOI：
10.1021/tx900110n
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发表时间：
2009-08
影响因子：
4.1
通讯作者：
Fishbein, James C.
中科院分区：
文献类型：
--
作者：
Holland, Ryan;Navamal, Mettachit;Velayutham, Murugesan;Zweier, Jay L.;Kensler, Thomas W.;Fishbein, James C.
三种二硫硫酮癌症化学预防剂 - 吡噻硫酮 1、茴香二硫酮 (ADT) 2、1,2-二硫醇-3-硫酮 (D3T) 3 和 1 的主要代谢物 4 - 在 hepa 1c1c7 细胞中诱导细胞保护酶 NQO1 的能力以及过氧化氢酶对此诱导的抑制作用已得到证实。 1、3 和4 形成O2• 的能力已被报道，这里证明2 在GSH 存在下分解，在添加硝酮自旋陷阱DMPO 后形成可通过epr 检测到的DMPO-OH 加合物。 2 在 GSH 存在下分解，在添加氢乙啶并在 510 nm 处激发后，会引发 580 nm 处的荧光，该荧光会因添加超氧化物歧化酶而减弱。化合物4是1的还原产物，证明2和3在硫醇盐和NaBH4等还原剂存在下分解，然后加入CH3I，形成S1-S2键还原断裂的二甲基化产物。用 2 或 3 处理的 Hepa 1c1c7 细胞在含有 CH3I 的缓冲液中裂解后，分离出相同的产物。在氩气气氛下，在乙醇水溶液中用 NaBH4 还原裂解 2 和 3，然后酸破坏剩余的硼氢化物，中和并引入 O2，导致 2 和 3 的重组程度分别为 80% 和 33%。总体数据与模型一致，其中二硫代硫酮通常在 Hepa 1c1c7 细胞中经历还原性裂解，从而产生 O2·，歧化为 H2O2，随后通过直接或间接方式影响转录因子 Nrf2 的核易位，从而上调第 2 相酶的表达。
The ability of three dithiolethione cancer chemopreventives - oltipraz 1, anetholedithione (ADT) 2, 1,2-dithiole-3-thione (D3T) 3 and the major metabolite, 4, of 1 - to induce the cytoprotective enzyme NQO1 in hepa 1c1c7 cells and the inhibition of this induction by catalase is demonstrated. The ability of 1, 3 and 4 to form O2• has been reported, and it is here demonstrated that 2 decomposes in the presence of GSH to form, upon addition of the nitrone spin trap DMPO, the DMPO-OH adduct that is detectable by epr. Decomposition of 2 in the presence of GSH elicits, upon the addition of hydroethidine and excitation at 510 nm, fluorescence at 580 nm that is diminished by the addition of superoxide dismutase. The compound 4, is product of reduction of 1 and it is demonstrated that 2 and 3 decompose in the presence of reductants such as thiolates and NaBH4, followed by addition of CH3I, to form the dimethylated products of reductive cleavage of the S1-S2 bond. The same products are isolated subsequent to lysis in buffer containing CH3I of Hepa 1c1c7 cells treated with 2 or 3. Reductive cleavage of 2 and 3 in aqueous ethanol by NaBH4 in an argon atmosphere, followed by acidic destruction of remaining borohydride and neutralization and introduction of O2 results in the reformation of 2 and 3 to the extent of 80 and 33%, respectively. The data in toto are consistent with a model in which dithiolethiones, generally, undergo reductive cleavage in Hepa 1c1c7 cells thereby resulting in the generation of O2• that dismutates to H2O2, that subsequently, by direct or indirect means, effects the nuclear translocation of transcription factor Nrf2, that upregulates phase 2 enzyme expression.
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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
影响因子：
4.1
作者：
Kim, W;Gates, KS
通讯作者：
Gates, KS
DOI：
10.1073/pnas.051632198
发表时间：
2001-03-13
影响因子：
11.1
作者：
Dinkova-Kostova, AT;Massiah, MA;Talalay, P
通讯作者：
Talalay, P
影响因子：
7.4
作者：
Han, Derick;Hanawa, Naoko;Kaplowitz, Neil
通讯作者：
Kaplowitz, Neil
影响因子：
1.8
作者：
Curphey, TJ;Libby, AH
通讯作者：
Libby, AH