farnesyl-pyrophosphate and pitavastatin
farnesyl-pyrophosphate has been researched along with pitavastatin* in 2 studies
Other Studies
2 other study(ies) available for farnesyl-pyrophosphate and pitavastatin
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Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells.
Statins have a neuroprotective effect in neurological diseases, a pleiotropic effect possibly related to blood-brain barrier (BBB) function. We investigated the effect of pitavastatin on barrier functions of an in vitro BBB model with primary cultures of rat brain capillary endothelial cells (RBEC). Pitavastatin increased the transendothelial electrical resistance (TEER), an index of barrier tightness of interendothelial tight junctions (TJs), at a concentration of 10(-8) M, and decreased the endothelial permeability for sodium fluorescein through the RBEC monolayer. The increase in TEER was significantly reduced in the presence of isoprenoid geranylgeranyl pyrophosphate, whereas farnesyl pyrophosphate had no effect on TEER. Our immunocytochemical and Western blot analyses revealed that treatment with pitavastatin enhanced the expression of claudin-5, a main functional protein of TJs. Our data indicate that pitavastatin strengthens the barrier integrity in primary cultures of RBEC. The BBB-stabilizing effect of pitavastatin may be mediated partly through inhibition of the mevalonate pathway and subsequent up-regulation of claudin-5 expression. Topics: Animals; Biomarkers; Blood-Brain Barrier; Brain; Cell Membrane Permeability; Cells, Cultured; Claudins; Electric Impedance; Endothelial Cells; Fluorescent Antibody Technique; Gene Expression Regulation; Polyisoprenyl Phosphates; Quinolines; Rats; RNA, Messenger; Sesquiterpenes; Tight Junctions | 2010 |
Effect of pitavastatin on transactivation of human serum paraoxonase 1 gene.
Hepatic hydroxymethyl glutary coenzyme A HMG-CoA reductase inhibitors (statins) have various anti atherosclerosis pleiotropic effects that are independent of cholesterol reduction. Human serum paraoxonase 1 (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidative modification of low-density lipoprotein (LDL). We investigated the effects of statins on PON1 gene transcription using a reporter gene assay. Promoter activity of the PON1 gene was estimated by measuring luciferase activity of plasmids with a PON1 promoter region transfected into human hepatoma HepG2 cells and human embryonic kidney (HEK) 293 cells. Pitavastatin, simvastatin, and atorvastatin each significantly increased PON1 promoter activity, and the transactivation by pitavastatin was abrogated by mevalonic acid and farnesyl pyrophosphate (FPP), however, not by geranylgeranyl pyrophosphate. Further, PON1 promoter activity was enhanced by farnesyl transferase inhibitor (FTI), but not by geranylgeranyl transferase inhibitor (GGTI). PON1 gene transcription has been reported to be dependent on Sp1 and the transactivation by pitavastatin was completely abrogated by mithramycin, an inhibitor of Sp1. Our results suggest that pitavastatin activates transcription of the PON1 gene through the FPP pathway, which may play an important role in the anti atherosclerotic effects of statins. Topics: Alkyl and Aryl Transferases; Aryldialkylphosphatase; Atorvastatin; Cell Line; Cell Nucleus; DNA; Dose-Response Relationship, Drug; Electrophoretic Mobility Shift Assay; Farnesyltranstransferase; Gene Expression Regulation, Enzymologic; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Luciferases; Mevalonic Acid; Plasmids; Polyisoprenyl Phosphates; Pyrroles; Quinolines; Sesquiterpenes; Sp1 Transcription Factor; Time Factors; Transcriptional Activation; Transfection | 2005 |