Preferential increase of glutathione S-transferase class alpha transcripts in cultured human hepatocytes by phenobarbital, 3-methylcholanthrene, and dithiolethiones.
Preferential increase of glutathione S-transferase class alpha transcripts in cultured human hepatocytes by phenobarbital, 3-methylcholanthrene, and dithiolethiones.
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苯巴比妥、3-甲基胆蒽和二硫烯硫酮优先增加培养的人肝细胞中谷胱甘肽 S-转移酶 α 类转录物。
作者：
F. Morel;O. Fardel;David J. Meyer;S. Langouet;Kim S. Gilmore;B. Meunier;Chen;T. Kensler;B. Ketterer
在啮齿动物中，多种化合物能够保护包括致癌物在内的各种外来物质的急性和慢性毒性，至少部分是通过诱导药物代谢酶包括谷胱甘肽S转移酶来实现的。我们提出的问题是，这些化合物是否也会在人体肝脏中诱导GST。原代培养的人肝细胞暴露于苯巴比妥、3-甲基胆蒽和两种二硫代硫酮[1，2-二硫杂-3-硫酮及其5-(2-吡津基)-4-甲基衍生物，奥替拉兹]，并用Northern印迹分析检测GSTα、Mu和pi类的稳态mRNA水平。每天处理3次后，两种二硫代硫酮是最有效的诱导剂；苯巴比妥也有效，但幅度较小，3-甲基胆蒽虽然刺激了所有细胞的细胞色素P-450 1A2 mRNA，但只在6个样本中的2个样本中增加了GST mRNA。无论是哪种化合物，只有GSTA1和/或A2转录本被诱导。GST M1mRNAs无反应或仅有轻微反应，而GSTP1mRNAs在对照细胞中大多检测不到，不受四种化学物质中任何一种处理的影响。GST A1和/或A2mRNAs的诱导水平存在较大的个体差异，不存在性别差异。这些结果清楚地表明，苯巴比妥、3-甲基胆蒽和二硫代硫酮能显著增加人肝细胞GST的mRNA水平，并且GSTα类优先参与其中。
In rodents, a diversity of compounds are able to protect against acute and chronic toxicities of various xenobiotics including carcinogens, at least in part through induction of drug-metabolizing enzymes including glutathione S-transferase (GST) enzymes. We have posed the question as to whether or not these compounds also induce GSTs in human liver. Primary human hepatocyte cultures were exposed to phenobarbital, 3-methylcholanthrene, and two dithiolethiones [1,2-dithiole-3-thione and its 5-(2-pyrazinyl)-4-methyl derivative, oltipraz], and steady-state mRNA levels of GST classes alpha, mu, and pi were determined by Northern blot analysis. After 3 daily treatments, the two dithiolethiones were the most potent inducers; phenobarbital was also effective but to a lesser extent and 3-methylcholanthrene increased GST mRNA in only 2 of the 6 samples, although it stimulated cytochrome P-450 1A2 mRNA in all cell preparations. Whatever the compound only GSTA1 and/or A2 transcripts were induced. GST M1 mRNAs were not responsive or only slightly responsive, and GST P1 mRNAs, which were mostly undetectable in control cells, were not affected by treatment with any of the four chemicals. Large individual variations were observed in the level of induction of GST A1 and/or A2 mRNAs, and no sex difference could be demonstrated. These results clearly indicate that phenobarbital, 3-methylcholanthrene, and dithiolethiones are able to markedly increase mRNA levels of GST in human hepatocytes and that the GST alpha class is preferentially involved.
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DOI：
10.1111/j.1432-1033.1990.tb19140.x
发表时间：
1990-07
期刊：
European journal of biochemistry
影响因子：
--
作者：
F. Morel;P. Beaune;D. Ratanasavanh;J. Flinois;C. Yang;F. Guengerich;A. Guillouzo
通讯作者：
F. Morel;P. Beaune;D. Ratanasavanh;J. Flinois;C. Yang;F. Guengerich;A. Guillouzo
人肝谷胱甘肽 S-转移酶基因超家族：Hb 亚基 cDNA 的表达和染色体作图。
影响因子：
14.9
作者：
DeJong,JL;Chang,CM;Whang-Peng,J;Knutsen,T;Tu,CP
通讯作者：
Tu,CP
人肝谷胱甘肽 S-转移酶：Ha 亚基 cDNA 的完整一级序列。
DOI：
10.1016/s0006-291x(86)80358-8
发表时间：
1986
影响因子：
3.1
作者：
Tu,CP;Qian,B
通讯作者：
Qian,B
饲喂 5-(2-吡嗪基)-4-甲基-1,2-二硫醇-3-硫酮（吡噻硫酮）及相关 1,2-二硫醇-3-硫酮和 1,2-二硫醇的大鼠抗黄曲霉毒素致瘤性的机制
影响因子：
11.2
作者：
Kensler,TW;Egner,PA;Dolan,PM;Groopman,JD;Roebuck,BD
通讯作者：
Roebuck,BD
大鼠谷胱甘肽 S-转移酶超基因家族。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lai,HC;Tu,CP
通讯作者：
Tu,CP