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首页> 外文期刊>Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research >Clioquinol is sulfated by human jejunum cytosol and SULT1A3, a human-specific dopamine sulfotransferase.
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Clioquinol is sulfated by human jejunum cytosol and SULT1A3, a human-specific dopamine sulfotransferase.

机译：人空肠细胞溶质和人特异性多巴胺磺基转移酶SULT1A3会硫酸化对苯二酚。

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摘要

Clioquinol, originally marketed as an oral intestinal amebicide, was widely used for multiple intestinal disorders. Its use as an oral agent was, however, discontinued because of its possible association with subacute myelo-optico-neuropathy or SMON. Meanwhile, its use for neurodegenerative diseases has recently been suggested. The metabolic fate of clioquinol, however, is poorly described. Since clioquinol is excreted as a sulfate in animals and humans, we have sought to identify a human sulfotransferase (SULT) responsible for the sulfation. We found that sulfating activities of human jejunal cytosols to clioquinol were well correlated with those to dopamine, a typical SULT1A3 substrate. Consistently, recombinant SULT1A3 showed the highest activity to clioquinol in vitro among the human SULTs examined. The S(50) value for the clioquinol sulfation by SULT1A3 was similar to the K(m) value for that by cytosols from human jejunum, where SULT1A3 is abundantly expressed. Moreover, clioquinol inhibited both human jejunal cytosol- and SULT1A3-mediated sulfations of dopamine in a dose-dependent manner, showing similar IC(50) values. These results suggest that SULT1A3, which is highly expressed in intestine but not in liver, is responsible for the clioquinol sulfation in humans, raising a possibility that orally administered clioquinol might inhibit dopamine sulfation in human intestines.
机译：最初以口服小肠安非他命的形式销售的喹喔啉酚已广泛用于多种肠道疾病。但是，由于其可能与亚急性骨髓性视神经炎或SMON相关联，因此不再用作口服药物。同时，最近已经提出将其用于神经退行性疾病。然而，关于氯喹醇的代谢命运描述得很少。由于氯喹啉在动物和人类中以硫酸盐的形式排泄，因此我们试图确定负责硫酸化的人磺基转移酶（SULT）。我们发现，人空肠溶质对氯喹醇的硫酸盐化活性与对多巴胺（一种典型的SULT1A3底物）的硫酸盐化作用密切相关。一致地，在所检查的人类SULT中，重组SULT1A3在体外对氯喹醇的活性最高。 SULT1A3产生的氯喹醇硫酸盐的S（50）值与人空肠中大量表达SULT1A3的胞质溶胶的K（m）值相似。此外，氯喹醇以剂量依赖性方式抑制人空肠溶质和SULT1A3介导的多巴胺的硫酸化，显示相似的IC（50）值。这些结果表明，SULT1A3在肠道中高表达，但在肝脏中却不表达，是造成人体中的氯喹醇硫酸化的原因，这增加了口服氯碘喹醇可能抑制人肠中多巴胺硫酸化的可能性。

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