Cholera Toxin Decreases SLC26A3 Expression and Function in Intestinal Epithelial Cells

다국어 초록 (Multilingual Abstract)

Down‐regulated in adenoma (DRA, SLC26A3), the major Cl−/HCO3− exchanger involved in electroneutral NaCl absorption in the mammalian intestine, has emerged as a novel therapeutic target for diarrhea. Diarrhea commonly involves decreased absorption and/or increased secretion of fluid and electrolytes. We and others have shown decreased expression and function of DRA in infectious diarrhea. In this regard, cholera toxin (CTX) secreted by Vibrio cholerae is one of the most potent agents causing infectious diarrhea. Whether DRA function/expression is altered in CTX‐induced diarrhea is not known. Therefore, the current studies were undertaken to examine the effects of CTX on DRA in vitro in intestinal epithelial Caco‐2 cells. DRA function (Cl−/HCO3− exchange activity) was measured as DIDS sensitive 125I− uptake, mRNA and protein levels were assessed by quantitative real‐time PCR and immunoblotting respectively. Our results showed that treatment of Caco‐2 cells with CTX (1, 5 and 10 ng/ml) for 24 h significantly decreased Cl−/HCO3− exchange activity in a dose dependent manner. Concomitant dose‐dependent decrease in DRA mRNA levels was observed in response to CTX [1 ng/ml (46.3 ± 8.8 % p< 0.0001), 5 ng/ml (69.5 ± 3.1 % P < 0.004) and 10 ng/ml (76.5 ± 2.1%, P< 0.02)] compared to untreated control. Similarly, DRA protein levels were also significantly decreased [1 ng/ml (39 ± 15.7 5% p< 0.0001), 5 ng/ml (60.8 ± 6.3 % P < 0.0001) and 10 ng/ml (56.7 ± 12.6%, P< 0.0001)]. In conclusion, our data suggest that CTX‐induced decrease in DRA expression and function could contribute to the pathophysiology of CTX‐induced diarrhea.
Support or Funding Information
(Supported by NIDDK/Department of Veteran Affairs)
This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.