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High sodium butyrate levels induce MDR1 activation in colorectal cells: Impact of 15-deoxy-Δ(12,14)-prostaglandin J(2) on the resistance to saquinavir.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2012 Feb 24; Vol. 418 (4), pp. 609-15. Date of Electronic Publication: 2012 Jan 24. - Publication Year :
- 2012
-
Abstract
- The bioavailability of HIV protease inhibitors is altered by P-glycoproteins (P-gp). The aim of this study was to elucidate the impact of sodium butyrate (NaBut), a unique product of the bacterial fermentation found in elevated concentrations in AIDS patients on P-gp expression. As prostaglandin production is upregulated under inflammatory conditions, we determined the role of 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) in the NaBut-induced P-gp functionality in colonic epithelial cells. Treatment with NaBut significantly increased MDR1 transcription and P-gp expression on the surface of both types of cells. Nevertheless, the addition of 15d-PGJ(2) to NaBut-stimulated cells significantly upregulated MDR1 mRNA expression and P-gp expression and functionality, leading to an important diminution of saquinavir accumulation by these cells. Our data provide evidence that both NaBut and prostaglandins may profoundly affect the intracellular accumulation of saquinavir in AIDS patients with compromised colonic walls.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
Caco-2 Cells
Humans
Intestinal Mucosa metabolism
Prostaglandin D2 metabolism
Transcription, Genetic drug effects
ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis
Butyrates pharmacology
Drug Resistance, Viral
HIV Protease Inhibitors pharmacology
Intestinal Mucosa drug effects
Prostaglandin D2 analogs & derivatives
Saquinavir pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 418
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 22293191
- Full Text :
- https://doi.org/10.1016/j.bbrc.2012.01.046