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Titolo:
ATP-binding cassette transporter A1 (ABCA1) affects total body sterol metabolism
Autore:
Drobnik, W; Lindenthal, B; Lieser, B; Ritter, M; Weber, TC; Liebisch, G; Giesa, U; Igel, M; Borsukova, H; Buchler, C; Fung-Leung, WP; Von Bergmann, K; Schmitz, G;
Indirizzi:
Univ Regensburg, Inst Klin Chem, D-93042 Regensburg, Germany Univ Regensburg Regensburg Germany D-93042 , D-93042 Regensburg, Germany Univ Regensburg, Lab Med, D-93042 Regensburg, Germany Univ Regensburg Regensburg Germany D-93042 , D-93042 Regensburg, Germany Univ Bonn, Dept Clin Pharmacol, D-5300 Bonn, Germany Univ Bonn Bonn Germany D-5300 Dept Clin Pharmacol, D-5300 Bonn, Germany RW Johnson Pharmaceut Res Inst, San Diego, CA 92121 USA RW Johnson Pharmaceut Res Inst San Diego CA USA 92121 Diego, CA 92121 USA
Titolo Testata:
GASTROENTEROLOGY
fascicolo: 5, volume: 120, anno: 2001,
pagine: 1203 - 1211
SICI:
0016-5085(200104)120:5<1203:ACTA(A>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
DENSITY-LIPOPROTEIN RECEPTOR; MDR1 P-GLYCOPROTEIN; CHOLESTEROL ABSORPTION; TANGIER-DISEASE; PLASMA-MEMBRANE; SR-BI; MICE; GENE; DEFICIENCY; HUMANS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Schmitz, G Univ Regensburg, Inst Klin Chem, Franz Josef Str Allee 11, D-93042 Regensburg, Germany Univ Regensburg Franz Josef Str Allee 11 Regensburg Germany D-93042
Citazione:
W. Drobnik et al., "ATP-binding cassette transporter A1 (ABCA1) affects total body sterol metabolism", GASTROENTY, 120(5), 2001, pp. 1203-1211

Abstract

Background & Aims: Members of the family of ABC transporters are involved in different processes of sterol metabolism, and ABCA1 was recently identified as a key regulator of high-density lipoprotein (HDL) metabolism. Our aim was to further analyze the role of ABCA1 in cholesterol metabolism. Methods: ABCA1-deficient mice (ABCA1(-/-)) and wild-type mice were compared for different aspects of sterol metabolism, Intestinal cholesterol absorption was determined by a dual stable isotope technique, and analysis of fecal, plasma, and tissue sterols was performed by gas chromatography/ mass spectrometry. Key regulators of sterol metabolism were investigated by Northern andWestern blot analyses or enzyme activity assays, Results: ABCA1-disrupted sv129/C57BL/6 hybrid mice showed a significant reduction in intestinal cholesterol absorption. The decrease in cholesterol absorption was followed by an enhanced fecal loss of neutral sterols, whereas fecal bile acid excretion was not affected. Total body cholesterol synthesis was significantly increased, with enhanced 3-hydroxy-3-methyglutaryl- coenzyme A (HMG-CoA) reductase observed in adrenals and spleen, In addition, ABCA1(-/-) mice showed markedly increased concentrations of cholesterol precursors in the plasma, lung, intestine, and feces, Reduced HMG-CoA reductase messenger RNA and enzyme activity in the liver suggest that enhanced cholesterol synthesis in ABCA1(-/-) mice occurs in peripheral tissues rather than the liver. Conclusions: The metabolism of cholesterol and cholesterol precursors is markedly affected by a lack of ABCA1 function.

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Documento generato il 27/11/20 alle ore 13:45:03