کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5860814 1133241 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clioquinol is sulfated by human jejunum cytosol and SULT1A3, a human-specific dopamine sulfotransferase
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Clioquinol is sulfated by human jejunum cytosol and SULT1A3, a human-specific dopamine sulfotransferase
چکیده انگلیسی

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 S50 value for the clioquinol sulfation by SULT1A3 was similar to the Km 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 IC50 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.

► Clioquinol is sulfated by SULT1A3 in human jejunum cytosols. ► Clioquinol inhibits SULT1A3-mediated dopamine sulfation in vitro. ► Clioquinol inhibits dopamine sulfation mediated by human jejunum cytosols in vitro. ► Orally administered clioquinol may inhibit dopamine sulfation in human intestines.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 206, Issue 2, 10 October 2011, Pages 229-233
نویسندگان
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