کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5500972 | 1534623 | 2017 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Zn2+-sensing receptor, ZnR/GPR39, upregulates colonocytic Clâ absorption, via basolateral KCC1, and reduces fluid loss
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The Zn2+-sensing receptor, ZnR/GPR39, upregulates colonocytic Clâ absorption, via basolateral KCC1, and reduces fluid loss The Zn2+-sensing receptor, ZnR/GPR39, upregulates colonocytic Clâ absorption, via basolateral KCC1, and reduces fluid loss](/preview/png/5500972.png)
چکیده انگلیسی
Administration of zinc, as a complement to oral rehydration solutions, effectively diminishes duration and severity of diarrhea, but it is not known whether it merely fulfills a nutritional deficiency, or if zinc has a direct role of regulating solute absorption. We show that Zn2+ acts via a specific receptor, ZnR/GPR39, to reduce fluid loss. Intestinal fluid secretion triggered by cholera toxin (CTx) was lower in WT mice compared to ZnR/GPR39 KO. In the absence of dietary Zn2+ we observed similar fluid accumulation in WT and ZnR/GPR39 KO mice, indicating that Zn2+ and ZnR/GPR39 are both required for a beneficial effect of Zn2+ in diarrhea. In primary colonocytes and in Caco-2 colonocytic cells, activation of ZnR/GPR39 enhanced Clâ transport, a critical factor in diarrhea, by upregulating K+/Clâ cotransporter (KCC1) activity. Importantly, we show basolateral expression of KCC1 in mouse and human colonocytes, thus identifying a novel Clâ absorption pathway. Finally, inhibition of KCC-dependent Clâ transport enhanced CTx-induced fluid loss. Altogether, our data indicate that Zn2+ acting via ZnR/GPR39 has a direct role in controlling Clâ absorption via upregulation of basolateral KCC1 in the colon. Moreover, colonocytic ZnR/GPR39 and KCC1 reduce water loss during diarrhea and may therefore serve as effective drug targets.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1863, Issue 4, April 2017, Pages 947-960
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1863, Issue 4, April 2017, Pages 947-960
نویسندگان
Laxmi Sunuwar, Hila Asraf, Mark Donowitz, Israel Sekler, Michal Hershfinkel,