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The budding yeast RENT complex, consisting of at least three proteins (Net1, Cdc14, Sir2), is anchored to the nucleolus by Net1. RENT controls mitotic exit, nucleolar silencing, and nucleolar localization of Nop1. Here, we report two new functions of Net1. First, Net1 directly binds Pol I and stimulates rRNA synthesis both in vitro and in vivo. Second, Net1(More)
Oseltamivir (Tamiflu, Roche, Nutley, NJ), an ester-type prodrug of the anti-influenza drug Ro 64-0802 (oseltamivir carboxylate), has been reported to be associated with neuropsychiatric side effects, which are likely to be caused by distribution of oseltamivir and/or its metabolite into the central nervous system. Enhanced toxicity and brain distribution of(More)
We previously showed that oseltamivir, a prodrug of the influenza virus neuraminidase inhibitor Ro 64-0802, is a substrate of proton-coupled oligopeptide transporter (PEPT1), and its intestinal absorption in rats is markedly inhibited by administration with milk. To investigate the importance of PEPT1 for oseltamivir absorption in humans, and the(More)
Oseltamivir, an ester-type prodrug of the neuraminidase inhibitor [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), has been developed for the treatment of A and B strains of the influenza virus but has neuropsychiatric and other side effects. In this study, we characterized the transport across intestinal(More)
In the present study, we analyzed the function of a novel mutation (c.1628T>G, p.Leu543Trp) in the solute carrier organic anion transporter (SLCO) 1B1 gene, encoding organic anion transporting polypeptide (OATP) 1B1, which was identified in a patient with pravastatin-induced myopathy. OATP1B1 variants carrying the mutation (OATP1B1*1a+c.1628T>G or(More)
OBJECTIVES We recently reported that flavanone aglycones (hesperetin, naringenin and eriodictyol) are efficiently absorbed via proton-coupled active transport, in addition to transcellular passive diffusion, in Caco-2 cells. Here, we aimed to evaluate in detail the absorption mechanisms of these flavanones, as well as homoeriodictyol and sakuranetin. (More)
Being the major pathway by which topically applied ophthalmic drugs enter the eye, the cornea can control the amount of active drug ultimately absorbed by offering resistance to drug permeation and by metabolizing the drug during permeation. This research seeks to determine the esterase activity in the cornea and two of its component layers--epithelium and(More)
Ezrin, radixin, and moesin (ERM) proteins regulate functional expression of certain transporters, but little is known about their effect on P-glycoprotein (P-gp). Here, we investigated the influence of ERM proteins on the expression and activity of P-gp at the transcriptional, translational, and posttranslational levels, using HepG2 as a model cell line.(More)
We have recently found that the frequency of OATP-C*15 is significantly higher in patients who experienced myopathy after receiving pravastatin or atorvastatin than in patients without myopathy. However, there were two patients who experienced pravastatin-induced myopathy despite the fact that they did not possess OATP-C*15 or other known mutations of(More)
Poly[2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate]s (PMBs) are water-soluble solid copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate with a molecular weight of 30,000 (PMB50T) or 100,000 (PMB100T). Here, we characterized the solubilizing properties of PMBs using miconazole (MCZ), vidarabine (Ara-A) and(More)