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dc.contributor.authorAndriamihaja, Mireille
dc.contributor.authorLan, Annaig
dc.contributor.authorBeaumont, Martin
dc.contributor.authorAudebert, Marc
dc.contributor.authorWong, Ximena
dc.contributor.authorYamada, Kana
dc.contributor.authorYin, Yulong
dc.contributor.authorTome, Daniel
dc.contributor.authorCarrasco-Pozo, Catalina
dc.contributor.authorGotteland, Martin
dc.contributor.authorKong, Xiangfeng
dc.contributor.authorBlachier, Francois
dc.description.abstractp-Cresol that is produced by the intestinal microbiota from the amino acid tyrosine is found at millimolar concentrations in the human feces. The effects of this metabolite on colonic epithelial cells were tested in this study. Using the human colonic epithelial HT-29 Glc–/+ cell line, we found that 0.8 mM p-cresol inhibits cell proliferation, an effect concomitant with an accumulation of the cells in the S phase and with a slight increase of cell detachment without necrotic effect. At this concentration, p-cresol inhibited oxygen consumption in HT-29 Glc–/+ cells. In rat normal colonocytes, p-cresol also inhibited respiration. Pretreatment of HT-29 Glc–/+ cells with 0.8 mM p-cresol for 1 day resulted in an increase of the state 3 oxygen consumption and of the cell maximal respiratory capacity with concomitant increased anion superoxide production. At higher concentrations (1.6 and 3.2 mM), p-cresol showed similar effects but additionally increased after 1 day the proton leak through the inner mitochondrial membrane, decreasing the mitochondrial bioenergetic activity. At these concentrations, p-cresol was found to be genotoxic toward HT-29 Glc–/+ and also LS-174T intestinal cells. Lastly, a decreased ATP intracellular content was observed after 3 days treatment. p-Cresol at 0.8 mM concentration inhibits colonocyte respiration and proliferation. In response, cells can mobilize their “respiratory reserve.” At higher concentrations, p-cresol pretreatment uncouples cell respiration and ATP synthesis, increases DNA damage, and finally decreases the ATP cell content. Thus, we have identified p-cresol as a metabolic troublemaker and as a genotoxic agent toward colonocytes.
dc.relation.ispartofjournalFree Radical Biology and Medicine
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Biochemistry and Metabolomics
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiochemistry & Molecular Biology
dc.subject.keywordsEndocrinology & Metabolism
dc.subject.keywordsIntestinal microbiota
dc.titleThe deleterious metabolic and genotoxic effects of the bacterial metabolite p-cresol on colonic epithelial cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationAndriamihaja, M; Lan, A; Beaumont, M; Audebert, M; Wong, X; Yamada, K; Yin, Y; Tome, D; Carrasco-Pozo, C; Gotteland, M; Kong, X; Blachier, F, The deleterious metabolic and genotoxic effects of the bacterial metabolite p-cresol on colonic epithelial cells, Free Radical Biology and Medicine, 2015, 85, pp. 219-227
gro.hasfulltextNo Full Text
gro.griffith.authorCarrasco Pozo, Catalina A.

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