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Titolo:
Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apoB-100 and triglyceride secretion from HepG2 cells
Autore:
Funatsu, T; Suzuki, K; Goto, M; Arai, Y; Kakuta, H; Tanaka, H; Yasuda, S; Ida, M; Nishijima, S; Miyata, K;
Indirizzi:
Inst Drug Discovery Res, Pharmacol Lab, Tsukuba, Ibaraki 3058585, Japan Inst Drug Discovery Res Tsukuba Ibaraki Japan 3058585 raki 3058585, Japan Inst Drug Discovery Res, Mol Med Lab, Tsukuba, Ibaraki 3058585, Japan InstDrug Discovery Res Tsukuba Ibaraki Japan 3058585 raki 3058585, Japan
Titolo Testata:
ATHEROSCLEROSIS
fascicolo: 1, volume: 157, anno: 2001,
pagine: 107 - 115
SICI:
0021-9150(200107)157:1<107:PIOCSB>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
HMG-COA REDUCTASE; APOLIPOPROTEIN-B SECRETION; LOW-DENSITY LIPOPROTEIN; TRANSFER PROTEIN; MICROSOMAL TRIGLYCERIDE; HAMSTER HEPATOCYTES; GENE-EXPRESSION; MINIATURE PIGS; EFFICACY; SIMVASTATIN;
Keywords:
HMG-CoA reductase inhibitor; apo B; HepG2 cells; cholesterol synthesis; atorvastatin; simvastatin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Funatsu, T Inst Drug Discovery Res, Pharmacol Lab, 21 Miyukigaoka, Tsukuba, Ibaraki 3058585, Japan Inst Drug Discovery Res 21 Miyukigaoka Tsukuba Ibaraki Japan 3058585
Citazione:
T. Funatsu et al., "Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apoB-100 and triglyceride secretion from HepG2 cells", ATHEROSCLER, 157(1), 2001, pp. 107-115

Abstract

Atorvastatin is a new HMG-CoA reductase inhibitor that strongly lowers plasma cholesterol and triglyceride (TG) levels in humans and animals. Since previous data indicated that atorvastatin has prolonged inhibition of hepatic cholesterol synthesis, we tested whether this longer duration of inhibitory effect on cholesterol synthesis decreased hepatic lipoprotein secretion in vitro. We used the HepG2 hepatoma cell line to: (1) determine the time required Lentil levels of secreted apo B-100 and TG declined significantly, (2) examine the relation to the mass of cellular cholesteryl ester (CE) and(3) test microsomal triglyceride transfer protein (MTP) activity which leads to decreased apo B-100 production. Although atorvastatin significantly inhibited cholesterol synthesis in,HepG2 cells regardless of treatment duration (1, 14 or 24 h). it did not inhibit TG synthesis. Apo B-100 and TG secretion were unchanged after 1-h atorvastatin treatment, but declined significantly after 24-h treatment. Atorvastatin treatment also reduced cellular CE mass, exhibiting both time- and dose-dependency. Mevalonolactone, a product of HMG-CoA reductase, attenuated the inhibitory effects of atorvastatin. Atorvastatin strongly reduced mRNA levels of MTP, whereas it did not inhibit MTP activity as measured by TG transfer assay between liposomes. Simvastatin also induced treatment- and time-dependent reductions in apo B-100. whereas the MTP inhibitor BMS-201038 exhibited no time dependency, instead inhibiting this variable even on I-h treatment. These results: indicate that reduced apo B-100 secretion caused by atorvastatin is: a secondary result owing to decreased lipid availability, and that atorvastatin's: efficacy depends on the duration of cholesterol synthesis inhibition in the liver. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 09:14:27