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Titolo:
Sterol regulatory element-binding protein-1 is regulated by glucose at thetranscriptional level
Autore:
Hasty, AH; Shimano, H; Yahagi, N; Amemiya-Kudo, M; Perrey, S; Yoshikawa, T; Osuga, J; Okazaki, H; Tamura, Y; Iizuka, Y; Shionoiri, F; Ohashi, K; Harada, K; Gotoda, T; Nagai, R; Ishibashi, S; Yamada, N;
Indirizzi:
Univ Tsukuba, Inst Clin Med, Dept Internal Med, Tsukuba, Ibaraki 3058575, Japan Univ Tsukuba Tsukuba Ibaraki Japan 3058575 sukuba, Ibaraki 3058575, Japan Univ Tokyo, Dept Metab Dis, Tokyo 1138655, Japan Univ Tokyo Tokyo Japan 1138655 kyo, Dept Metab Dis, Tokyo 1138655, Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 40, volume: 275, anno: 2000,
pagine: 31069 - 31077
SICI:
0021-9258(20001006)275:40<31069:SREPIR>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYUNSATURATED FATTY-ACIDS; LIPOPROTEIN RECEPTOR PROMOTER; LIPOGENIC GENE-EXPRESSION; SREBP-1C MESSENGER-RNA; DIFFERENTIATION FACTOR-1; SYNTHASE PROMOTER; CULTURED-CELLS; INSULIN; LIVERS; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Shimano, H Univ Tsukuba, Inst Clin Med, Dept Internal Med, 1-1-1 Tennodai,Tsukuba, Ibaraki 3058575, Japan Univ Tsukuba 1-1-1 Tennodai Tsukuba Ibaraki Japan 3058575 Japan
Citazione:
A.H. Hasty et al., "Sterol regulatory element-binding protein-1 is regulated by glucose at thetranscriptional level", J BIOL CHEM, 275(40), 2000, pp. 31069-31077

Abstract

In vivo studies suggest that sterol regulatory element-binding protein (SREBP)-1 plays a key role in the upregulation of lipogenic genes in the livers of animals that have consumed excess amounts of carbohydrates. In light of this, we sought to use an established mouse hepatocyte cell line, H2-35, to further define the mechanism by which glucose regulates nuclear SREBP-1 levels, First, we show that these cells transcribe high levels of SREBP-1c that are increased 4-fold upon differentiation from a prehepatocyte to a hepatocyte phenotype, making them an ideal cell culture model for the study of SREBP-1c induction. Second, we demonstrate that the presence of precursorand mature forms of SREBP-1 protein are positively regulated by medium glucose concentrations ranging from 5.5 to 25 mM, and are also regulated by insulin, with the amount of insulin in the fetal bovine serum being sufficient for maximal stimulation of SREBP-1 expression. Third, we show that the increase in SREBP-1 protein is due to an increase in SREBP-1 mRNA, Reporter gene analysis of the SREBP-1c promoter demonstrated a glucose-dependent induction of transcription. In contrast, expression of a fixed amount of the precursor form of SREBP-1c protein showed that glucose does not influence itscleavage. Fourth, we demonstrate that the glucose induction of SREBP couldnot be reproduced by fructose, xylose, or galactose nor by glucose analogsa-deoxy glucose and 3-O-methyl glucopyranose. These data provide strong evidence for the induction of SREBP-1c mRNA by glucose leading to increased mature protein in the nucleus, thus providing a potential mechanism for the up-regulation of lipogenic genes by glucose in vivo.

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Documento generato il 03/04/20 alle ore 20:37:39