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Titolo:
NK-104, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, decreases apolipoprotein B-100 secretion from Hep G2 cells
Autore:
Ooyen, C; Zecca, A; Bersino, AM; Catapano, AL;
Indirizzi:
Univ Milan, Inst Pharmacol Sci, I-20133 Milan, Italy Univ Milan Milan Italy I-20133 Inst Pharmacol Sci, I-20133 Milan, Italy Ctr Studio Prevenz & Terapia Vasculopatie Aterosc, Milan, Italy Ctr StudioPrevenz & Terapia Vasculopatie Aterosc Milan Italy an, Italy
Titolo Testata:
ATHEROSCLEROSIS
fascicolo: 1, volume: 145, anno: 1999,
pagine: 87 - 95
SICI:
0021-9150(199907)145:1<87:NAP3CA>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHOLESTERYL ESTER SYNTHESIS; APO-B SECRETION; INTRACELLULAR DEGRADATION; HEPATIC SECRETION; STORAGE DISEASE; OLEIC-ACID; A-I; LIPOPROTEINS; STIMULATION; OLEATE;
Keywords:
statins; triglycerides; lipid synthesis; pulse-chase; ELISA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Catapano, AL Univ Milan, Inst Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy Univ Milan Via Balzaretti 9 Milan Italy I-20133 Milan, Italy
Citazione:
C. Ooyen et al., "NK-104, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, decreases apolipoprotein B-100 secretion from Hep G2 cells", ATHEROSCLER, 145(1), 1999, pp. 87-95

Abstract

Intracellular cholesterol biosynthesis may play a key role in supplying cholesterol (as cholesteryl ester) for the neutral core of very low density lipoprotein (VLDL), thus modulating the secretion of apolipoprotein B-100 (apo B-100) from hepatocytes. The effect of compound NK-104 was studied, a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA-reductase), on apo B-100 synthesis and secretion from the human hepatoma cell line Hep G2. Cells were preincubated with NK-104 (0.01-5 mu M) in the presence or absence of oleate (0.8 mM). Apo B-100 in the medium was determined by an enzyme-linked immunosorbent assay (ELISA). Incubation of Hep G2 with NK-104 resulted in a marked inhibition of cholesterogenesis (up to 95%), determined as incorporation of [C-14]acetate into sterols, and decreased in a dose-dependent manner apo B-100 secretion, both in basal conditions (from 110 to 82 ng/mg cell protein, P < 0.01) and after incubation with oleate (from 227 to 165 ng/mg cell protein, P < 0.01). Density gradient for distribution of a-po B-100 secreted, showed that this decrease was essentially due to a reduction of apo B-100 associated with lipoproteins in the density range of low density lipoproteins (LDL). Pulse-chase experiment demonstrated that NK-104 did not affect the synthetic rate of apo B-100 but increased intracellular degradation of newly synthesized protein. The compound had only marginal effect on the mass of intracellular triglyceride but significantly decreased intracellular mass of free cholesterol and cholesteryl ester (P < 0.01). It is speculated that the ability of compound NK-104 todecrease apo B-100 secretion from Hep G2 cells is due to a decreased intracellular cholesterol availability. (C) 1999 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 04/04/20 alle ore 08:43:09