High sodium butyrate levels induce MDR1 activation in colorectal cells: Impact of 15-deoxy-螖^12,14-prostaglandin J₂ on the resistance to saquinavir

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• 作者：Stamatoula Pasvanis ; Sarah Tremblay ; Nancy Dumais ; ^{nancy.dumais@usherbrooke.ca}
• 关键词：P-glycoprotein ; MDR1 ; Sodium butyrate ; 15d-PGJ2 ; HIV ; Saquinavir
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：24 February, 2012
• 卷：418
• 期：4
• 页码：609-615
• 文件大小：591 K

摘要

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-螖^12,14-prostaglandin J₂ (15d-PGJ₂) 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-PGJ₂ 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.