The effect of oxidative stress upon the intestinal epithelial uptake of butyrate

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Gonçalves P (Author) FMUP; Gregorio, I (Author) Other; Catarino, TA (Author) Other; Martel, F (Author) FMUP

Journal

Title: European Journal of Pharmacology

Vol. 699

Pages: 88-100

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 23 Citations

Other information

Authenticus ID: P-002-17W

DOI: 10.1016/j.ejphar.2012.11.029

Abstract (EN): Our aim was to investigate the effect of oxidative stress upon butyrate uptake at the intestinal epithelial level. For this, IEC-6 cells were treated with tert-butylhydroperoxide 3000 mu M (tBOOH), which increased levels of oxidative stress biomarkers, while maintaining cellular viability. The effect of tBOOH upon uptake of [C-14]butyrate ([C-14]BT) (10 mu M) can be summarized as follows: (a) it caused a reduction in the intracellular accumulation of [C-14]BT over time, (b) it strongly reduced total [C-14]BT uptake but did not affect Na+-independent uptake of [C-14]BT, and (c) it did not affect the kinetics of [C-14]BT uptake at 37 degrees C, but increased uptake at 4 degrees C. Moreover, tBOOH increased the efflux of [C-14]BT not mediated by breast cancer resistance protein. We thus conclude that tBOOH strongly inhibits Na+-coupled monocarboxylate cotransporter 1 (SMCT1)-mediated, but not H+-coupled monocarboxylate transporter (MCT1)-mediated butyrate uptake; moreover, it increases uptake and efflux of butyrate by passive diffusion. tBOOH did not affect the mRNA expression levels of MCT1 and SMCT1 nor their cell membrane insertion. Rather, its effect was dependent on extracellular signal regulated kinase 112 and protein tyrosine kinase activation and on the generation of reactive oxygen species by NADPH and xanthine oxidases and was partially prevented by the polyphenols quercetin and resveratrol. In conclusion, tBOOH is an effective inhibitor of SMCT1-mediated butyrate transport in non-tumoral intestinal epithelial cells. Given the important role played by butyrate in the intestine, this mechanism may contribute to the procarcinogenic and proinflammatory effect of oxidative stress at this level.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13