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金属与螯合剂之间的相互作用会影响谷氨酸在脑突触膜上的结合。

Interaction between metals and chelating agents affects glutamate binding on brain synaptic membranes.

作者信息

Soares Félix Antunes, Farina Marcelo, Santos Francielli Weber, Souza Diogo, Rocha João Batista Teixeira, Nogueira Cristina Wayne

机构信息

Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, RS, Brazil.

出版信息

Neurochem Res. 2003 Dec;28(12):1859-65. doi: 10.1023/a:1026175825871.

DOI:10.1023/a:1026175825871
PMID:14649728
Abstract

The present study investigates the possible effects of Hg2+, Pb2+, and Cd2+ on [3H]-glutamate binding. To better understand the role of the thiol-disulfide status on the toxicity of such metals toward glutamatergic neurotransmission, we used three thiol chelating agents, 2,3-dimercaptopropanol (BAL), 2,3-dimercaptopropane 1-sulfonate (DMPS), and meso-2,3-dimercaptosuccinic acid (DMSA). Dithiotreitol (DTT) was tested for its ability to prevent metals-induced inhibition on [3H]-glutamate binding. Hg2+, Pb2+, and Cd2+ showed a concentration-dependent inhibition on [3H]-glutamate binding, and mercury was the most effective inhibitor. BAL did not prevent [3H]-glutamate binding inhibition by Hg2+, Cd2+, and Pb2+. However, DMPS and DMSA prevented the inhibition caused by Cd2+ and Pb2+, but not by Hg2+. DTT did not prevent the inhibition on [3H]-glutamate binding caused by 10 microM Hg2+. In contrast, it was able to partially prevent [3H]-glutamate binding inhibition caused by 40 microM Pb2+ and Cd2+. These results demonstrated that the heavy metals present an inhibitory effect on [3H]-glutamate binding. In addition, BAL was less effective to protect [3H]-glutamate binding inhibition caused by these metals than other chelating agents studied.

摘要

本研究调查了Hg2+、Pb2+和Cd2+对[3H]-谷氨酸结合的可能影响。为了更好地理解硫醇-二硫键状态在此类金属对谷氨酸能神经传递毒性中的作用,我们使用了三种硫醇螯合剂,2,3-二巯基丙醇(BAL)、2,3-二巯基丙烷1-磺酸盐(DMPS)和内消旋-2,3-二巯基琥珀酸(DMSA)。测试了二硫苏糖醇(DTT)防止金属诱导的对[3H]-谷氨酸结合抑制的能力。Hg2+、Pb2+和Cd2+对[3H]-谷氨酸结合表现出浓度依赖性抑制,汞是最有效的抑制剂。BAL不能防止Hg2+、Cd2+和Pb2+对[3H]-谷氨酸结合的抑制。然而,DMPS和DMSA可防止Cd2+和Pb2+引起的抑制,但不能防止Hg2+引起的数据抑制。DTT不能防止10微摩尔Hg2+对[3H]-谷氨酸结合的抑制。相反,它能够部分防止40微摩尔Pb2+和Cd2+对[3H]-谷氨酸结合的抑制。这些结果表明,重金属对[3H]-谷氨酸结合具有抑制作用。此外,与所研究的其他螯合剂相比,BAL在保护[3H]-谷氨酸结合免受这些金属引起的抑制方面效果较差。

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