Ousingsawat, Jiraporn and Mirza, Myriam and Tian, Yuemin and Roussa, Eleni and Schreiber, Rainer and Cook, David I. and Kunzelmann, Karl (2011) Rotavirus toxin NSP4 induces diarrhea by activation of TMEM16A and inhibition of Na+ absorption. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 461 (5). pp. 579-589. ISSN 0031-6768,
Full text not available from this repository. (Request a copy)Abstract
Rotavirus infection is the most frequent cause for severe diarrhea in infants, killing more than 600,000 every year. The nonstructural protein NSP4 acts as a rotavirus enterotoxin, inducing secretory diarrhea without any structural organ damage. Electrolyte transport was assessed in the colonic epithelium from pups and adult mice using Ussing chamber recordings. Western blots and immunocytochemistry was performed in intestinal tissues from wild-type and TMEM16A knockout mice. Ion channel currents were recorded using patch clamp techniques. We show that the synthetic NSP4(114-135) peptide uses multiple pro-secretory pathways to induce diarrhea, by activating the recently identified Ca2+-activated Cl- channel TMEM16A, and by inhibiting Na+ absorption by the epithelial Na+ channel ENaC and the Na+/glucose cotransporter SGLT1. Activation of secretion and inhibition of Na+ absorption by NSP4(114-135), respectively, could be potently suppressed by wheat germ agglutinin which probably competes with NSP4(114-135) for binding to an unknown glycolipid receptor. The present paper gives a clue as to mechanisms of rotavirus-induced diarrhea and suggests wheat germ agglutinin as a simple and effective therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AGE-DEPENDENT DIARRHEA; BRUSH-BORDER MEMBRANE; ION-TRANSPORT; NONSTRUCTURAL GLYCOPROTEIN; INTRACELLULAR CALCIUM; ELECTROLYTE TRANSPORT; ENTEROTOXIN; CHANNELS; VIRUS; EXPRESSION; Rotavirus; NSP4; Ca2+-activated Cl- channels; TMEM16A; ENaC; Epithelial Na+ channels; SGLT1; Colonic epithelium; Diarrhea |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jun 2020 08:13 |
| Last Modified: | 22 Jun 2020 08:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20922 |
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