Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells.

S. Morikawa, M. Umetani, S. Nakagawa, H. Yamazaki, H. Suganami, K. Inoue, M. Kitahara, T. Hamakubo, T. Kodama, Y. Saito

Research output: Contribution to journalArticle

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Abstract

The effect of various 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the induction of HMG-CoA reductase and low density lipoprotein (LDL) receptor mRNA were quantitatively determined in the cultured human hepatoma cell line Hep G2 by means of a ribonuclease protection assay. Lipophilic inhibitors including mevastatin, simvastatin, atorvastatin and NK-104 were able to increase the levels of mRNAs for HMG-CoA reductase and the LDL receptor, but the hydrophilic inhibitor pravastatin was not effective in Hep G2 cells as had previously been reported. The LDL receptor mRNA was induced by NK-104 most effectively between 0.1 to 10 microM among the lipophilic inhibitors, whereas the degrees of induction of HMG-CoA reductase mRNA by these inhibitors did not differ significantly from each other. When cells were treated with a 200-fold excess of the IC50 concentration of each inhibitor, NK-104 was able to induce LDL receptor mRNA most effectively. These results indicate that the effect of HMG-CoA reductase inhibitors on the upregulation of mRNA for reductase and LDL receptor are different from each other and among these lipophilic inhibitors. NK-104 is most effective in inducing LDL receptor mRNA in Hep G2 cells.

Original languageEnglish (US)
Pages (from-to)138-144
Number of pages7
JournalJournal of Atherosclerosis and Thrombosis
Volume7
Issue number3
StatePublished - 2000

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Hydroxymethylglutaryl CoA Reductases
LDL Receptors
Cultured Cells
Oxidoreductases
Cells
Messenger RNA
Hep G2 Cells
Pravastatin
Simvastatin
Ribonucleases
3-hydroxy-3-methylglutaryl-coenzyme A
Inhibitory Concentration 50
Hepatocellular Carcinoma
Assays
Up-Regulation
pitavastatin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Internal Medicine
  • Biochemistry, medical

Cite this

Morikawa, S., Umetani, M., Nakagawa, S., Yamazaki, H., Suganami, H., Inoue, K., ... Saito, Y. (2000). Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. Journal of Atherosclerosis and Thrombosis, 7(3), 138-144.

Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. / Morikawa, S.; Umetani, M.; Nakagawa, S.; Yamazaki, H.; Suganami, H.; Inoue, K.; Kitahara, M.; Hamakubo, T.; Kodama, T.; Saito, Y.

In: Journal of Atherosclerosis and Thrombosis, Vol. 7, No. 3, 2000, p. 138-144.

Research output: Contribution to journalArticle

Morikawa, S, Umetani, M, Nakagawa, S, Yamazaki, H, Suganami, H, Inoue, K, Kitahara, M, Hamakubo, T, Kodama, T & Saito, Y 2000, 'Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells.', Journal of Atherosclerosis and Thrombosis, vol. 7, no. 3, pp. 138-144.
Morikawa, S. ; Umetani, M. ; Nakagawa, S. ; Yamazaki, H. ; Suganami, H. ; Inoue, K. ; Kitahara, M. ; Hamakubo, T. ; Kodama, T. ; Saito, Y. / Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. In: Journal of Atherosclerosis and Thrombosis. 2000 ; Vol. 7, No. 3. pp. 138-144.
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