Differential activation and inhibition of different forms of rat liver glutathione S-transferase by the herbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T).

Differential activation and inhibition of different forms of rat liver glutathione S-transferase by the herbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T).
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除草剂 2,4-二氯苯氧基乙酸酯 (2,4-D) 和 2,4,5-三氯苯氧基乙酸酯 (2,4,5-T) 对不同形式的大鼠肝脏谷胱甘肽 S-转移酶的差异激活和抑制。

DOI:
10.1016/0041-008x(84)90101-7
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发表时间:
1984
影响因子:
3.8
通讯作者:
Boyer,TD
Boyer,TD
中科院分区:
医学3区
文献类型:
--
作者:
Vessey,DA;Boyer,TD

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The predominant forms of the dimeric enzyme glutathione S-transferase were purified from rat liver. Forms YbY′band YbYb(also known as forms C and A, respectively) could be almost completely inhibited by 2,4-dichlorophenoxyacetate (2,4-D). Half-maximal inhibition was obtained at 0.5 mm 2,4-D. Inhibition was seen even at extrapolated infinite concentrations of both substrates for YbYbbut not YbY′b. These same forms could also be inhibited 70 to 80% by 2,4,5-trichlorophenoxyacetate (2,4,5-T) with half maximal inhibition occurring at 0.2 mm. Glutathione S-transferase from YaYawas maximally inhibited by 72 and 30%, respectively, by 2,4-D and 2,4,5-T. The 30% inhibition of YaYacaused by 2,4,5-T was shown to reduce the nearly complete inhibition caused by a previously characterized inhibitor, namely bile acids. This suggests competition for a common binding site on the enzyme. In contrast to the above results, it was found that form YcYc(also termed AA) was activated 2.7-fold by 2,4,5-T and 1.4-fold by 2,4-D. This activation could be blocked by chenodeoxycholate which, by itself, did not affect the activity of the enzyme. The effects of 2,4,5-T and 2,4-D on the heterodimer YaYc(also termed form B) were intermediate between their effects on YaYaand YcYc, suggesting that each subunit contributes its unique property to the heterodimer. The microsomal membrane-bound form of glutathione S-transferase was also examined and found to be inhibited by both 2,4-D and 2,4,5-T. However, unlike the inhibitions of soluble forms, 2,4,5-T caused more extensive inhibition than 2,4-D. It is concluded that exposure to 2,4-D and 2,4,5-T can limit the ability of glutathione S-transferase forms YbYband YbY′bto metabolize electrophilic toxins. This capacity to potentiate the toxicity of certain electrophiles indicates a need to study the effect of herbicides on glutathione S-transferases from human tissues.
DOI: --
发表时间: 1982
期刊: European journal of biochemistry / FEBS
影响因子: --
作者:
Morgenstern,R;Guthenberg,C;Depierre,JW
通讯作者: Depierre,JW
胆汁酸抑制谷胱甘肽 S-转移酶。
DOI: 10.1042/bj1970321
发表时间: 1981
期刊: The Biochemical journal
影响因子: --
作者:
D. Vessey;D. Zakim
通讯作者: D. Zakim
配体异质性:两个不相同的亚基是两个不同蛋白质的单体的证据。
DOI: --
发表时间: 1977
期刊: Biochimica et Biophysica Acta
影响因子: --
作者:
N. Bass;R. Kirsch;S. Tuff;I. Marks;S. Saunders
通讯作者: S. Saunders
大鼠肝脏谷胱甘肽 S-转移酶的结构、功能和杂交研究。
DOI: 10.1016/0006-2952(83)90048-5
发表时间: 1983
影响因子: 5.8
作者:
T. Boyer;W. Kenney;D. Zakim
通讯作者: D. Zakim
大鼠静脉注射后 2,4,5-三氯苯氧基乙酸的剂量依赖性药代动力学特征。
DOI: 10.1016/0041-008x(76)90228-3
发表时间: 1976
影响因子: 3.8
作者:
M. W. Sauerhoff;W. Braun;G. Blau;P. J. Gehring
通讯作者: P. J. Gehring