Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke (QC), Canada J1K 2R1.
Biochem Biophys Res Commun. 2012 Feb 24;418(4):609-15. doi: 10.1016/j.bbrc.2012.01.046. Epub 2012 Jan 24.
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.
HIV 蛋白酶抑制剂的生物利用度受 P-糖蛋白（P-gp）的影响。本研究旨在阐明丁酸纳（NaBut）对 P-gp 表达的影响。丁酸纳是在 AIDS 患者体内含量升高的细菌发酵的独特产物。由于在炎症条件下前列腺素的产生会被上调，因此我们确定了 15-脱氧-Δ（12,14）-前列腺素 J2（15d-PGJ2）在 NaBut 诱导的结肠上皮细胞中 P-gp 功能中的作用。NaBut 的处理显着增加了两种细胞表面的 MDR1 转录和 P-gp 表达。然而，将 15d-PGJ2 添加到 NaBut 刺激的细胞中可显着上调 MDR1 mRNA 表达和 P-gp 表达和功能，导致这些细胞中 saquinavir 的积累显着减少。我们的数据提供了证据，表明丁酸纳和前列腺素都可能严重影响受损结肠壁的 AIDS 患者体内 saquinavir 的细胞内积累。
