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Titolo:
Regulation of cholesterol 7 alpha-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXR alpha)
Autore:
Chiang, JYL; Kimmel, R; Stroup, D;
Indirizzi:
NE Ohio Univ, Coll Med, Dept Biochem & Mol Biol, Rootstown, OH 44272 USA NE Ohio Univ Rootstown OH USA 44272 m & Mol Biol, Rootstown, OH 44272 USA
Titolo Testata:
GENE
fascicolo: 1-2, volume: 262, anno: 2001,
pagine: 257 - 265
SICI:
0378-1119(20010110)262:1-2<257:ROC7AG>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEAR RECEPTOR; X-RECEPTOR; BILE-ACIDS; DIETARY-CHOLESTEROL; SIGNALING PATHWAY; HEPG2 CELLS; COUP-TFII; EXPRESSION; PROMOTER; LIGANDS;
Keywords:
bile acid synthesis; reverse cholesterol transport; cytochrome P450; nuclear receptors; gene regulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Chiang, JYL NE Ohio Univ, Coll Med, Dept Biochem & Mol Biol, POB 95, Rootstown, OH 44272 USA NE Ohio Univ POB 95 Rootstown OH USA 44272 stown, OH 44272 USA
Citazione:
J.Y.L. Chiang et al., "Regulation of cholesterol 7 alpha-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXR alpha)", GENE, 262(1-2), 2001, pp. 257-265

Abstract

The cholesterol 7 alpha -hydroxylase gene (CYP7A1) plays an important rolein regulation of bile acid biosynthesis and cholesterol homeostasis. Oxysterol receptor, LXR, stimulates, whereas the bile acid receptor, FXR, inhibits CYP7A1 transcription. The goal of this study was to investigate the roleof LXR alpha on the regulation of rat, human and hamster CYP7A1 transcription in its native promoter and cellular context. Cotransfection with LXR alpha and RXR alpha expression plasmids strongly stimulated rat CYP7A1/luciferase reporter activity in HepG2 cells and oxysterol was not required. However, LXR alpha had much less effect on hamster and no significant effect on human CYP7A1 promoter activity in HepG2 cells. In Chinese hamster ovary cells, cotransfection with LXR alpha stimulated reporter activity by less than2-fold and addition of 22(R)-hydroxycholesterol caused a small but significant stimulation of rat, human and hamster CYP7A1 promoter activity. At least two direct repeats of AGGTCA-like sequences with 4-base spacing (DR4) and five-base spacing (DR5), in previously identified bile acid response elements of the rat CYP7A1 were able to bind LXR alpha /RXR alpha and confer LXR alpha stimulation. However, LXR alpha did not bind to the corresponding sequences of the human gene and bound weakly to hamster and mouse DR4 sequences. Therefore, rats and mice have the unusual capacity to convert cholesterol to bile acids by LXR alpha -mediated stimulation of CYP7A1 transcription, whereas other species do not respond to cholesterol and develop hypercholesterolemia on a diet high in cholesterol. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/08/20 alle ore 19:57:24