کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9018403 | 1128702 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin
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کلمات کلیدی
BSPOATPbromosulfophthalein - برومواسولفوفلئالینtaurocholate - تاوروکولاتorganic anion transport - حمل آنیون آلیTransport - حمل و نقل یا ترابریBlood–brain barrier - سد خونی مغزیEnvironmental toxins - سموم زیست محیطیNatural toxins - سموم طبیعیNeurotoxicity - سمیت عصبیHepatotoxicity - سمیت کبدCyanobacteria - سیانوباکتریهاMicrocystin - میکروتیستینmicrocystin-LR - میکروسیستین LRHepatocyte - هپاتوسیت
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin](/preview/png/9018403.png)
چکیده انگلیسی
Microcystins are toxins produced by freshwater cyanobacteria. They are cyclic heptapeptides that exhibit hepato- and neurotoxicity. However, the transport systems that mediate uptake of microcystins into hepatocytes and across the blood-brain barrier have not yet been identified. Using the Xenopus laevis oocyte expression system we tested whether members of the organic anion transporting polypeptide superfamily (rodent: Oatps; human: OATPs) are involved in transport of the most common microcystin variant microcystin-LR by measuring uptake of a radiolabeled derivative dihydromicrocystin-LR. Among the tested Oatps/OATPs, rat Oatp1b2, human OATP1B1, human OATP1B3, and human OATP1A2 transported microcystin-LR 2- to 5-fold above water-injected control oocytes. This microcystin-LR transport was inhibited by co-incubation with the known Oatp/OATP substrates taurocholate (TC) and bromosulfophthalein (BSP). Microcystin-LR transport mediated by the human OATPs was further characterized and showed saturability with increasing microcystin-LR concentrations. The apparent Km values amounted to 7 ± 3 μM for OATP1B1, 9 ± 3 μM for OATP1B3, and 20 ± 8 μM for OATP1A2. No microcystin-LR transport was observed in oocytes expressing Oatp1a1, Oatp1a4, and OATP2B1. These results may explain some of the observed organ-specific toxicity of microcystin-LR. Oatp1b2, OATP1B1, and OATP1B3 are responsible for microcystin transport into hepatocytes, whereas OATP1A2 mediates microcystin-LR transport across the blood-brain barrier.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 203, Issue 3, 15 March 2005, Pages 257-263
Journal: Toxicology and Applied Pharmacology - Volume 203, Issue 3, 15 March 2005, Pages 257-263
نویسندگان
W.J. Fischer, S. Altheimer, V. Cattori, P.J. Meier, D.R. Dietrich, B. Hagenbuch,