GSH/GSSG redox couple plays central role in aryl hydrocarbon receptor‐dependent modulation of cytochrome P450 1A1

GSH/GSSG redox couple plays central role in aryl hydrocarbon receptor‐dependent modulation of cytochrome P450 1A1
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GSH/GSSG 氧化还原对在细胞色素 P450 1A1 芳烃受体依赖性调节中发挥核心作用

DOI:
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发表时间:
2018
影响因子:
3.6
通讯作者:
A. Mohammadi
A. Mohammadi
中科院分区:
医学4区
文献类型:
--
作者:
M. Omidi;Ali Ghafarian;A. Mohammadi

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芳香烃受体(AHR)靶基因的氧化还原调节,如最好的表征,细胞色素P450 1A 1(CYP 1A 1)还不知道。因此,本研究的目的是探索细胞氧化还原状态如何影响CYP 1A 1转录和酶活性的AHR依赖性调节。将携带CYP 1A 1反应元件的雄性BALB/c白化病小鼠、HepG 2细胞和人肝癌细胞系(HepG 2-XRE-Luc)暴露于建议的AHR内源性配体6-甲酰吲哚[3,2-B]咔唑(FICZ)单独或与丁硫氨酸-(S,R)-亚砜亚胺(BSO)或N-乙酰基-L-半胱氨酸(NAC)联合给药。CYP 1A 1转录和酶活性与谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)氧化还原对变化之间存在明确联系。在体内和体外的研究结果表明,AHR激活/抑制的时间过程的特点是在GSH/GSSG比例的增加/减少。基于这些发现,我们提出许多环境污染物和氧化剂通过改变细胞内氧化还原电位可能干扰AHR靶基因的正常功能。
The redox regulation of aryl hydrocarbon receptor (AHR) target genes such as the best characterized, cytochrome P450 1A1 (CYP1A1) has not been known. Therefore the aim of this study was to explore how cellular redox state can influence on AHR‐dependent modulation of CYP1A1 transcription and enzyme activities. Male BALB/c albino mice, HepG2 cells, and human hepatoma cell line (HepG2‐XRE‐Luc) carrying CYP1A1 response elements were exposed to suggested endogenous ligand of AHR,6‐formylindolo[3,2‐b] carbazole (FICZ) alone or in combination with, buthionine‐(S,R)‐sulfoximine (BSO) or N‐acetyl‐l‐cysteine (NAC). A clear link between CYP1A1 transcription and enzyme activity and changes in the glutathione/oxidised glutathione (GSH/GSSG) redox couple was shown. In vivo and in vitro findings demonstrated that the time course of AHR activation/inhibition is characterized by an increase/decrease in the GSH/GSSG ratio. Based on these findings, we propose that many environmental pollutants and oxidants by alteration in the intracellular redox potential may interfere with the normal function of AHR target genes.
DOI: 10.1016/j.freeradbiomed.2005.09.023
发表时间: 2006-01-01
影响因子: 7.4
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DOI: 10.1006/abbi.1998.0851
发表时间: 1998
期刊: Archives of biochemistry and biophysics.
影响因子: --
作者:
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