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• W2894913047 abstract "Vitamin C is an antioxidant and acts as a cofactor for many enzymatic reactions. Humans obtain vitamin C from dietary sources via intestinal absorption, a process that involves the sodium-dependent vitamin C transporters-1 and -2 (SVCT1 and SVCT2). Enterotoxigenic Escherichia coli (ETEC) infection impacts intestinal absorption/secretory functions, but nothing is known about its effect on ascorbic acid (AA) uptake. Here we demonstrate that infection of Caco-2 cells with ETEC led to a significant inhibition in intestinal AA uptake. This inhibition was associated with a marked reduction in hSVCT1 and hSVCT2 protein, mRNA, and heterogeneous nuclear RNA (hnRNA) expression levels as well as significant inhibition in the activity of both the SLC23A1 and SLC23A2 promoters. Similarly, exposure of mice to ETEC led to a significant inhibition in intestinal AA uptake and reduction in mSVCT1 and mSVCT2 protein, mRNA, and hnRNA expression levels. Inhibition was caused by the action of heat labile enterotoxin (LT), since infecting Caco-2 cells with LT-deficient ETEC (ΔLT) failed to impact AA uptake. Because LT activates adenylate cyclase, we also examined the effect of dibutyryl-cAMP in AA uptake by Caco-2 cells and observed a significant inhibition. Furthermore, treating the cells with celastrol, a specific NF-κB inhibitor, significantly blocked the inhibition of AA uptake caused by ETEC infection. Together, these data demonstrate that ETEC infection impairs intestinal AA uptake through a cAMP-dependent NF-κB-mediated pathway that regulates both SLC23A1 and SLC23A2 transcription. NEW & NOTEWORTHY Our findings demonstrate that heat-labile enterotoxin produced by enterotoxigenic Escherichia coli inhibits AA uptake in intestinal epithelial cells and mouse intestine. This effect is mediated through transcriptional repression of SLC23A1 (SVCT1) and SLC23A2 (SVCT2) via a cAMP-dependent NF-κB signaling pathway." @default.
• W2894913047 created "2018-10-12" @default.
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• W2894913047 date "2019-01-01" @default.
• W2894913047 modified "2023-10-18" @default.
• W2894913047 title "EnterotoxigenicEscherichia coliheat labile enterotoxin inhibits intestinal ascorbic acid uptake via a cAMP-dependent NF-κB-mediated pathway" @default.
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• W2894913047 doi "https://doi.org/10.1152/ajpgi.00259.2018" @default.
• W2894913047 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6383388" @default.
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• W2894913047 hasPublicationYear "2019" @default.
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