Reference - Detail
| RRC ID | 42246 |
|---|---|
| Author | Fan P, Zhang B, Kuroki S, Saku K. |
| Title | Pitavastatin, a potent hydroxymethylglutaryl coenzyme a reductase inhibitor, increases cholesterol 7 alpha-hydroxylase gene expression in HepG2 cells. |
| Journal | Circ J |
| Abstract |
BACKGROUND:The effect of pitavastatin on the mRNA levels of apolipoprotein (apo) A-I, peroxisome proliferator-activated receptor alpha (PPARalpha), cholesterol 7alpha-hydroxylase (CYP7A1), and farnesoid X receptor (FXR) in HepG2 cells was examined to establish whether pitavastatin affects bile acid synthesis and if so, to determine a possible molecular mechanism. METHODS AND RESULTS:HepG2 cells were cultured in serum-free Dulbecco's modified Eagle medium for 18 h before drug treatment. Total RNA was extracted at set times and mRNA levels were quantified by reverse transcription-real time polymerase chain reaction. Pitavastatin at 0.1, 1, 5, and 10 micromol/L increased the mRNA levels of apo A-I, PPARalpha, CYP7A1, and FXR in a dose-dependent manner. The mRNA levels of apo A-I, PPAR alpha, CYP7A1, and FXR similarly increased with increasing doses of pitavastatin. Coincubation of mevalonate (4 mmol/L) with pitavastatin (5 micromol/L) reversed the inductive effects of pitavastatin on the mRNA levels of these genes, indicating that the inductive effects of pitavastatin were related to its inhibition of HMG-CoA reductase. CONCLUSIONS:Pitavastatin increased the mRNA levels of CYP7A1 in HepG2 cells, suggesting that increased conversion of cholesterol to bile acids may be the mechanism for its potent low-density lipoprotein cholesterol-lowering effects. |
| Volume | 68(11) |
| Pages | 1061-6 |
| Published | 2004-11-1 |
| DOI | 10.1253/circj.68.1061 |
| PII | JST.JSTAGE/circj/68.1061 |
| PMID | 15502389 |
| MeSH | Apolipoprotein A-I / genetics Cell Line, Tumor Cholesterol 7-alpha-Hydroxylase / genetics Cholesterol 7-alpha-Hydroxylase / metabolism* DNA-Binding Proteins / genetics Dose-Response Relationship, Drug Enzyme Inhibitors / administration & dosage Enzyme Inhibitors / pharmacology* Gene Expression / drug effects Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* Mevalonic Acid / pharmacology PPAR alpha / genetics Quinolines / administration & dosage Quinolines / antagonists & inhibitors Quinolines / pharmacology* RNA, Messenger / metabolism Receptors, Cytoplasmic and Nuclear Transcription Factors / genetics |
| IF | 2.54 |
| Times Cited | 12 |
| WOS Category | CARDIAC & CARDIOVASCULAR SYSTEMS |
| Resource | |
| Human and Animal Cells | Hep G2(RCB0459) |