In vitro effect of arsenical compounds on glutathione-related enzymes
In vitro effect of arsenical compounds on glutathione-related enzymes
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DOI：
10.1021/tx000123x
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发表时间：
2001-05-01
影响因子：
4.1
通讯作者：
Snow, ET
中科院分区：
文献类型：
--
作者：
Chouchane, S;Snow, ET
砷毒性的机制被认为是由于亚砷酸盐（As-III）结合蛋白质硫醇的能力。谷胱甘肽（GSH）是细胞内最丰富的巯基，GSH及其相关酶都是重要的抗氧化剂，在砷等致癌物的解毒中发挥重要作用。砷对使用谷胱甘肽的各种酶的活性的影响已经使用来自酵母和牛谷胱甘肽过氧化物酶（GPx）和马谷胱甘肽S-转移酶（GST）的谷胱甘肽还原酶（GR）的纯化制剂测定。研究了增加浓度（从1 μ M到100 mM）的商业亚砷酸钠（As-III）和砷酸钠（As-V）以及制备的砷（III）-谷胱甘肽络合物[As-III（GS）（3）]和二碘化甲基砷（CH 3AsIII）对酶活性的影响。GR、GPx和GST对As-V不敏感（IC 50> 50 mM），并且没有一种酶被生理相关浓度的As-III、As-III（GS）（3）或CH 3-As-III抑制或激活，尽管CH 3 AsIII是最有效的抑制剂（0.3 mM <IC 50 < 1.5 mM）。GPx对砷处理最敏感，GST最不敏感。我们的研究结果并不涉及直接相互作用的谷胱甘肽相关酶，GR，GPx和GST，砷毒性的机制。CH 3AsIII是最有效的抑制剂，但目前尚不清楚是否砷代谢产物在关键靶组织中以足够高的浓度产生，以在砷毒性或致癌作用中发挥主要作用。
The mechanism of arsenic toxicity is believed to be due to the ability of arsenite (As-III) to bind protein thiols. Glutathione (GSH) is the most abundant cellular thiol, and both GSH and GSH-related enzymes are important antioxidants that play an important role in the detoxification of arsenic and other carcinogens. The effect of arsenic on the activity of a variety of enzymes that use GSH has been determined using purified preparations of glutathione reductase (GR) from yeast and bovine glutathione peroxidase (GPx) and equine glutathione S-transferase (GST). The effect on enzyme activity of increasing concentrations (from 1 muM to 100 mM) of commercial sodium arsenite (As-III) and sodium arsenate (As-V) and a prepared arsenic(III)-glutathione complex [As-III(GS)(3)] and methylarsenous diiodide (CH3AsIII) has been examined. GR, GPx, and GST are not sensitive to As-V (IC50 > 50 mM), and none of the enzymes are inhibited or activated by physiologically relevant concentrations of As-III, As-III(GS)(3), or CH3-As-III, although CH3AsIII is the most potent inhibitor (0.3 mM < IC50 < 1.5 mM). GPx is the most sensitive to arsenic treatment and GST the least. Our results do not implicate a direct interaction of As with the glutathione-related enzymes, GR, GPx, and GST, in the mechanism of arsenic toxicity. CH3AsIII is the most effective inhibitor, but it is unclear whether this product of arsenic metabolism is produced at a sufficiently high concentration in critical target tissues to play a major role in either arsenic toxicity or carcinogenesis.