کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9110800 | 1568752 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
TNF-α down-regulates the Na+-K+ ATPase and the Na+-K+-2Clâcotransporter in the rat colon via PGE2
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
علوم غدد
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چکیده انگلیسی
TNF-α is believed to play a pivotal role in the pathogenesis of inflammatory bowel diseases which have diarrhea as one of their symptoms. This work studies the effect of the cytokine on electrolyte and water movements in the rat distal colon using an intestinal perfusion technique and attempts to determine its underlying mechanism of action. TNF-α inhibited net water and chloride absorption, down-regulated in both surface and crypt colonocytes the Na+-K+-2Clâ cotransporter, and reduced the protein expression and activity of the Na+-K+ ATPase. Indomethacin up-regulated the pump and the cotransporter in surface cells but not in crypt cells, and in its presence, TNF-α could not exert its effect, suggesting an involvement of PGE2 in the cytokine action. The effect of TNF-α on the pump and symporter was studied also in cultured Caco-2 cells in isolation of the effect of other cells and tissues, to test whether the cytokine acts directly on intestinal cells. In these cells, TNF-α and PGE2 had a similar effect on the pump expression and activity as that observed in crypt cells but were without any effect on the Na+-K+-2Clâ cotransporter. It was concluded that the effect of the cytokine on colonocytes is mediated via PGE2. By inhibiting the Na+-K+ ATPase, it reduces the Na+ gradient needed for NaCl absorption, and by down-regulating the expression of the Na+-K+-2Clâ symporter, it reduces basolateral Clâ entry and luminal Clâ secretion. The inhibitory effect on absorption is more significant than the inhibitory effect on secretion resulting in a decrease in net electrolyte uptake and consequently in more water retention in the lumen.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cytokine - Volume 30, Issue 6, 21 June 2005, Pages 319-327
Journal: Cytokine - Volume 30, Issue 6, 21 June 2005, Pages 319-327
نویسندگان
Sarine Markossian, Sawsan Ibrahim Kreydiyyeh,