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Titolo:
7-ketocholesterol is an endogenous modulator for the arylhydrocarbon receptor
Autore:
Savouret, JF; Antenos, M; Quesne, M; Xu, J; Milgrom, E; Casper, RF;
Indirizzi:
CHU Niveau 3, INSERM, U135, Hop Bicetre, F-94270 Le Kremlin Bicetre, France CHU Niveau 3 Le Kremlin Bicetre France F-94270 e Kremlin Bicetre, France Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp Toronto ON Canada M5G 1X5 Inst, Toronto, ON M5G 1X5, Canada Univ Toronto, Dept Zool, Toronto, ON M5G 1A1, Canada Univ Toronto TorontoON Canada M5G 1A1 Zool, Toronto, ON M5G 1A1, Canada
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 5, volume: 276, anno: 2001,
pagine: 3054 - 3059
SICI:
0021-9258(20010202)276:5<3054:7IAEMF>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ARYL-HYDROCARBON RECEPTOR; LOW-DENSITY-LIPOPROTEIN; CHOLESTEROL OXIDATION-PRODUCTS; HUMAN MONOCYTE-MACROPHAGES; AH RECEPTOR; 7-ALPHA-HYDROXYCHOLESTEROL DEHYDROGENASE; ACTIVATION; OXYSTEROLS; TOXICITY; DIOXIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Savouret, JF CHU Niveau 3, INSERM, U135, Hop Bicetre, 78 Rue Gen Leclerc, F-94270 Le Kremlin Bicetre, France CHU Niveau 3 78 Rue Gen Leclerc Le Kremlin Bicetre France F-94270
Citazione:
J.F. Savouret et al., "7-ketocholesterol is an endogenous modulator for the arylhydrocarbon receptor", J BIOL CHEM, 276(5), 2001, pp. 3054-3059

Abstract

We have identified 7-ketocholesterol (7-KC) as an endogenous modulator that inhibits transactivation by the arylhydrocarbon receptor (AhR) through competitive binding against xenobiotic ligands. 7-KC binds AhR and displaces labeled dioxin (2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD)). IC50 is 5 x 10(-7) M in vivo and 7 x 10(-6) M in vitro. These figures are consistent withits concentration in human blood plasma and tissues. Association with 7-KCprevents AhR binding to DNA. 7-KC blocks the TCDD-mediated transactivationof stably expressed reporter gene constructs in T47-D cells as well as theexpression of the endogenous CYP 1A1 gene in HepG2 cells and in primary porcine aortic endothelial cells. Injection of 7-KC to rats blocks the induction of CYP 1A1 messenger RNA and protein in endothelial cells from myocardial blood vessels. The differential sensitivity of mammalian species to toxic effects of AhR ligands, especially dioxin (TCDD), correlates with the expression of 7-hydroxycholesterol dehydrogenase, which synthesizes 7-KC from 7-hydroxycholesterol. The documented involvement of AhR ligands in cardiovascular diseases through lipid peroxidation and endothelium dysfunction can now be examined in the context of displacement of this protective modulator.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/02/20 alle ore 09:37:33