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首页> 外文期刊>Archives of Toxicology >Reduction of arginase I activity and manganese levels in the liver during exposure of rats to methylmercury: a possible mechanism.
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Reduction of arginase I activity and manganese levels in the liver during exposure of rats to methylmercury: a possible mechanism.

机译:大鼠甲基汞暴露过程中肝脏精氨酸酶I活性和锰水平的降低:一种可能的机制。

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摘要

The toxicity of methylmercury (MeHg) is, in part, thought to be due to its interaction with thiol groups in a variety of enzymes, but the molecular targets of MeHg are poorly understood. Arginase I, an abundant manganese (Mn)-binding protein in the liver, requires Mn as an essential element to exhibit maximal enzyme activity. In the present study, we examined the effect of MeHg on hepatic arginase I in vivo and in vitro. Subcutaneous administration of MeHg (10 mg/kg) for 8 days to rats resulted in marked suppression of arginase I activity. With purified arginase I, we found that interaction of MeHg with arginase I caused the aggregation of arginase I as evaluated by centrifugation and subsequent precipitation, and then the reduction of catalytic activity. Experiments with organomercury column confirmed that arginase I has reactive thiols that are covalently bound to organomercury. While MeHg inhibited arginase I activity, Mn ions were released from this enzyme. These results suggest that MeHg-mediated suppression of hepatic arginase I activity in vivo is, at least in part, attributable to covalent modification of MeHg or substantial leakage of Mn ions from the active site.
机译:甲基汞(MeHg)的毒性在某种程度上被认为是由于其与多种酶中硫醇基的相互作用所致,但人们对甲基汞的分子靶标了解甚少。精氨酸酶I是肝脏中丰富的锰(Mn)结合蛋白,需要Mn作为必需元素才能发挥最大的酶活性。在本研究中,我们研究了MeHg在体内和体外对肝精氨酸酶I的影响。对大鼠皮下注射MeHg(10 mg / kg)8天导致精氨酸酶I活性受到明显抑制。使用纯化的精氨酸酶I,我们发现MeHg与精氨酸酶I的相互作用导致了精氨酸酶I的聚集,这通过离心和随后的沉淀进行评估,然后降低了催化活性。用有机汞柱进行的实验证实,精氨酸酶I具有与有机汞共价结合的反应性硫醇。尽管MeHg抑制了精氨酸酶I的活性,但该酶释放了Mn离子。这些结果表明,MeHg介导的体内对肝精氨酸酶I活性的抑制至少部分归因于MeHg的共价修饰或活性部位中Mn离子的大量泄漏。

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