Relative Induction of mRNA for HMG CoA Reductase and LDL Receptor by Five Different HMG-CoA Reductase Inhibitors in Cultured Human Cells

Morikawa, Shigeru; Umetani, Michihisa; Nakagawa, Shunji; Yamazaki, Hiroyuki; Suganami, Hideki; Inoue, Kenji; Kitahara, Masaki; Hamakubo, Takao; Kodama, Tatsuhiko; Saitō, Yasushi

doi:10.5551/jat1994.7.138

Cited by 72 publications

(53 citation statements)

References 31 publications

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“…It produced 23% to 33% and 38% to 47% reductions in total and LDL cholesterol levels, respectively, in patients with hyperlipidemia in a clinical trial [10][11][12][13][14][15][16] . Levels of LDL receptor mRNA and HMG-CoA mRNA were significantly higher in Hep G2 cells treated with pitavastatin than those treated with atorvastatin 17) . Although several results obtained in experimental animals support the hypothesis that the increased hepatic LDL receptor activity brought about by reductase inhibitors may be beneficial for the clearance of LDL cholesterol, in human subjects, little evidence of this has been obtained.…”

Section: Cholesterol-lowering Effectsmentioning

confidence: 83%

Efficacy of a Low Dose of Pitavastatin Compared with Atorvastatin in Primary Hyperlipidemia: Results of a 12-week, open label study

Yoshitomi¹,

Ishii

Kaneki³

et al. 2006

JAT

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Section: Cholesterol-lowering Effectsmentioning

confidence: 83%

Efficacy of a Low Dose of Pitavastatin Compared with Atorvastatin in Primary Hyperlipidemia: Results of a 12-week, open label study

Yoshitomi¹,

Ishii

Kaneki³

et al. 2006

JAT

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“…14 C]-acetate into non-saponifiable lipids by applying Cohen's method (19) with some modifications (20).…”

Section: Determination Of Cholesterol Synthesismentioning

confidence: 99%

Analysis of the Global RNA Expression Profiles of Skeletal Muscle Cells Treated with Statins

Morikawa

Murakami

Yamazaki

et al. 2005

JAT

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“…As a result of statin treatment, intracellular cholesterol concentrations are decreased, which leads to activation of the transcription factor, sterol responsive element-binding protein-2 (SREBP2), which regulates several genes controlling cholesterol homeostasis, including low-density lipoprotein (LDL) receptor (12,13). Plasma LDL concentrations are decreased as a consequence of increased LDL clearance.…”

Section: Introductionmentioning

confidence: 99%

Pitavastatin Increases ABCA1 Expression by Dual Mechanisms: SREBP2-Driven Transcriptional Activation and PPARα-Dependent Protein Stabilization but Without Activating LXR in Rat Hepatoma McARH7777 Cells

et al. 2011

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Abstract. Hepatic ATP-binding cassette transporter A1 (ABCA1) plays a key role in high-density lipoprotein (HDL) production by apolipoprotein A-I (ApoA-I) lipidation. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, increase ABCA1 mRNA levels in hepatoma cell lines, but their mechanism of action is not yet clear. We investigated how statins increase ABCA1 in rat hepatoma McARH7777 cells. Pitavastatin, atorvastatin, and simvastatin increased total ABCA1 mRNA levels, whereas pravastatin had no effect. Pitavastatin also increased ABCA1 protein. Hepatic ABCA1 expression in rats is regulated by both liver X receptor (LXR) and sterol regulatory element-binding protein (SREBP2) pathways. Pitavastatin repressed peripheral type ABCA1 mRNA levels and its LXR-driven promoter, but activated the liver-type SREBPdriven promoter, and eventually increased total ABCA1 mRNA expression. Furthermore, pitavastatin increased peroxisome proliferator-activated receptor α (PPARα) and its downstream gene expression. Knockdown of PPARα attenuated the increase in ABCA1 protein, indicating that pitavastatin increased ABCA1 protein via PPARα activation, although it repressed LXR activation. Furthermore, the degradation of ABCA1 protein was retarded in pitavastatin-treated cells. These data suggest that pitavastatin increases ABCA1 protein expression by dual mechanisms: SREBP2-mediated mRNA transcription and PPARα-mediated ABCA1 protein stabilization, but not by the PPAR-LXR-ABCA1 pathway.

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Relative Induction of mRNA for HMG CoA Reductase and LDL Receptor by Five Different HMG-CoA Reductase Inhibitors in Cultured Human Cells

Cited by 72 publications

References 31 publications

Efficacy of a Low Dose of Pitavastatin Compared with Atorvastatin in Primary Hyperlipidemia: Results of a 12-week, open label study

Efficacy of a Low Dose of Pitavastatin Compared with Atorvastatin in Primary Hyperlipidemia: Results of a 12-week, open label study

Analysis of the Global RNA Expression Profiles of Skeletal Muscle Cells Treated with Statins

Pitavastatin Increases ABCA1 Expression by Dual Mechanisms: SREBP2-Driven Transcriptional Activation and PPARα-Dependent Protein Stabilization but Without Activating LXR in Rat Hepatoma McARH7777 Cells

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