title: 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.
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.
authors.affiliation: Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke (QC), Canada J1K 2R1.
authors.forename: Stamatoula
authors.initials: S
authors.lastname: Pasvanis
authors.forename: Sarah
authors.initials: S
authors.lastname: Tremblay
authors.forename: Nancy
authors.initials: N
authors.lastname: Dumais
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D002087:Butyrates / Q000494:pharmacology*; D018938:Caco-2 Cells; D024882:Drug Resistance, Viral; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D019258:Saquinavir / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002087:Butyrates; D017320:HIV Protease Inhibitors; D019258:Saquinavir; D015230:Prostaglandin D2