POST-TRANSCRIPTIONAL REGULATION OF THE ABC TRANSPORTERS MRP2, BCRP AND P-GP IN ENTEROCYTES DURING ACUTE ACETAMINOPHEN (APAP) INTOXICATION IN MICE.

RUDRAIAH S; ORBEA L; GHANEM CI; MANAUTOU JE

New Orleans

Congreso; 55 Annual Meeting and ToxExp; 2016

Society of Toxicology

We have previously described the transcriptional regulation of ABC transporters in liver and brain in reponse to APAP treatment. The aim of the present work was to study the apical ABC transporters expression in the small intestine (Mrp2, Bcrp and P-gp) during APAP intoxication. For this purpose, male C57BL6 mice were given APAP (400mg/kg, i.p.) or vehicle. All sections of the small intestine were removed at 6, 12, 24 or 48 h after treatment. At 24 and 48 h, intestinal Mrp2, Bcrp and P-gp protein expression was determined by Western blotting using brush border membrane only. mRNA expression for these ABC transporters was also assayed by qRT-PCR at 6, 12 and 24 h. Immunohistochemical analysis of Mrp2, Bcrp and P-gp was also performed. Protein expression of Mrp2, Bcrp and P-gp was significantly increased in the proximal region of the intestine of APAP treated mice by 153%; 208% and 149%, respectively. By 48 h, Mrp2, Bcrp and P-gp protein expression returned to basal values, which is consistent with immunohistochemical analysis as well. Interestingly, the mRNA expression of any of these ABC transporters was not different between APAP and vehicle groups at any of the time points examined. In conclusion, our data demonstrates that during APAP intoxication in mice, the protein expression of the apical ABC transporters (Mrp2, Bcrp and P-gp) was up-regulated in the intestine of mice. The lack of changes in mRNA expression of these transporters is indicative of a post-transcriptional regulation mechanism that is as yet unresolved.