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Titolo: A role for smooth endoplasmic reticulum membrane cholesterol ester in determining the intracellular location and regulation of sterol-regulatory-element-binding protein-2
Autore: Iddon, CR; Wilkinson, J; Bennett, AJ; Bennett, J; Salter, AM; Higgins, JA;
- Indirizzi:
- Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2TN S Yorkshire, England Univ Nottingham, Queens Med Ctr, Dept Biomed Sci, Nottingham NG7 2UH, England Univ Nottingham Nottingham England NG7 2UH , Nottingham NG7 2UH, England Univ Nottingham, Sch Biosci, Div Nutr Biochem, Loughborough LE12 5RD, Leics, England Univ Nottingham Loughborough Leics England LE12 5RD 2 5RD, Leics, England
- Titolo Testata:
- BIOCHEMICAL JOURNAL
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volume: 358,
anno: 2001,
parte:, 2
pagine: 415 - 422
- SICI:
- 0264-6021(20010901)358:<415:ARFSER>2.0.ZU;2-E
- Fonte:
- ISI
- Lingua:
- ENG
- Soggetto:
- CLEAVAGE-ACTIVATING PROTEIN; BOUND TRANSCRIPTION FACTOR; LOW-DENSITY LIPOPROTEINS; MESSENGER-RNA LEVELS; APOLIPOPROTEIN-B; RABBIT HEPATOCYTES; TRANSGENIC MICE; CELL-MEMBRANES; CULTURED-CELLS; APO-B;
- Keywords:
- acyl-CoA : cholesterol acyltransferase; cholesterol feeding; HMG-CoA reductase; LDL receptor; simvastatin;
- Tipo documento:
- Article
- Natura:
- Periodico
- Settore Disciplinare:
- Life Sciences
- Citazioni:
- 49
- Recensione:
- Indirizzi per estratti:
- Indirizzo: Higgins, JA Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN,S Yorkshire, England Univ Sheffield Sheffield S Yorkshire England S10 2TN England
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- Citazione:
- C.R. Iddon et al., "A role for smooth endoplasmic reticulum membrane cholesterol ester in determining the intracellular location and regulation of sterol-regulatory-element-binding protein-2", BIOCHEM J, 358, 2001, pp. 415-422
Abstract
Cellular cholesterol homoeostasis is regulated through proteolysis of the membrane-bound precursor sterol-regulatory-element-binding protein (SREBP) that releases the mature transcription factor form, which regulates gene expression. Our aim was to identify the nature and intracellular site of the putative sterol-regulatory pool which regulates SREBP proteolysis in hamster liver. Cholesterol metabolism was modulated by feeding hamsters control chow, or a cholesterol-enriched diet, or by treatment with simvastatin or with the oral acyl-CoA : cholesterol acyltransferase inhibitor C1-1011 plus cholesterol. The effects of the different treatments on SREBP activation were confirmed by determination of the mRNAs for the low-density lipoprotein receptor and hydroxymethylglutaryl-CoA (HMG-CoA) reductase and by measurement of HMG-CoA reductase activity. The endoplasmic reticulum was isolated from livers and separated into subfractions by centrifugation in self-generating iodixanol gradients. Immunodetectable SREBP-2 accumulated in the smooth endoplasmic reticulum of cholesterol-fed animals. Cholesterol ester levels of the smooth endoplasmic reticulum membrane (but not the cholesterol levels) increased after cholesterol feeding and fell after treatment with simvastatin or C1-1011. The results suggest that an increased cellular cholesterol load causes accumulation of SREBP-2 in the smooth endoplasmic reticulum and, therefore, that membrane cholesterol ester may be one signal allowing exit of the SREBP-2/SREBP-cleavage-regulating protein complex to the Golgi.
ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/21 alle ore 12:47:00