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Titolo:
Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2) - Promoter analysis and role of the peroxisome proliferator-activated receptor PPAR alpha
Autore:
Fourcade, S; Savary, S; Albet, S; Gauthe, D; Gondcaille, C; Pineau, T; Bellenger, J; Bentejac, M; Holzinger, A; Berger, J; Bugaut, M;
Indirizzi:
Univ Bourgogne, Fac Sci Gabriel, Biol Cellulaire & Mol Lab, F-21000 Dijon,France Univ Bourgogne Dijon France F-21000 aire & Mol Lab, F-21000 Dijon,France INRA, Lab Pharmacol & Toxicol, F-31931 Toulouse, France INRA Toulouse France F-31931 armacol & Toxicol, F-31931 Toulouse, France Univ Bourgogne, UPRES Lipides & Nutr, Dijon, France Univ Bourgogne DijonFrance rgogne, UPRES Lipides & Nutr, Dijon, France Dr v Hauner Childrens Hosp, Mol Biol & DNA Diagnost Lab, Munich, Germany Dr v Hauner Childrens Hosp Munich Germany Diagnost Lab, Munich, Germany Univ Vienna, Brain Res Inst, A-1010 Vienna, Austria Univ Vienna Vienna Austria A-1010 Brain Res Inst, A-1010 Vienna, Austria
Titolo Testata:
EUROPEAN JOURNAL OF BIOCHEMISTRY
fascicolo: 12, volume: 268, anno: 2001,
pagine: 3490 - 3500
SICI:
0014-2956(200106)268:12<3490:FIOTAG>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
X-LINKED ADRENOLEUKODYSTROPHY; COA OXIDASE GENE; FATTY-ACIDS; RESPONSE ELEMENT; MEMBRANE-PROTEIN; FUNCTIONAL INTERACTIONS; GENOMIC ORGANIZATION; RETINOIC ACID; CDNA CLONING; EXPRESSION;
Keywords:
ABC transporters; adrenoleukodystrophy (ALD); fibrate; peroxisome proliferator-activated receptor alpha (PPAR alpha); promoter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Bugaut, M Univ Bourgogne, Fac Sci Gabriel, Biol Cellulaire & Mol Lab, 6 BdGabriel, F-21000 Dijon, France Univ Bourgogne 6 Bd Gabriel Dijon France F-21000 Dijon, France
Citazione:
S. Fourcade et al., "Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2) - Promoter analysis and role of the peroxisome proliferator-activated receptor PPAR alpha", EUR J BIOCH, 268(12), 2001, pp. 3490-3500

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease due to a defect in the ABCD1 (ALD) gene. ABCD1, and the two close homologues ABCD2 (ALDR) and ABCD3 (PMP70), are genes encoding ATP-binding cassette half-transporters of the peroxisomal membrane. As overexpression of the ABCD2 or ABCD3 gene can reverse the biochemical phenotype of X-ALD (reduced beta -oxidation of very-long-chain fatty acids), pharmacological induction of thesepartially redundant genes may represent a therapeutic approach to X-ALD. We previously reported that the ABCD2 and ABCD3 genes could be strongly induced by fibrates, which are hypolipidaemic drugs and peroxisome-proliferators in rodents. We provide evidence that the induction is dependent on peroxisome proliferator-activated receptor (PPAR alpha) as both genes were not induced in fenofibrate-treated PPAR alpha -/- knock-out mice. To further characterize the PPAR alpha pathway, we cloned and analysed the promoter of theABCD2 gene, the closest homologue of the ABCD1 gene. The proximal region (2 kb) of the rat promoter displayed a high conservation with the human and mouse cognate sequences suggesting an important role of the region in regulation of the ABCD2 gene. Classically, fibrate-induction involves interaction of PPAR alpha with a response element (PPRE) characterized by a direct repeat of the AGGTCA-like motif. Putative PPRE motifs of the rat ABCD2 promoter were studied in the isolated form or in their promoter context by gel-shift assay and transfection of COS-7 cells. We failed to characterize a functional PPRE, suggesting a different mechanism for the PPAR alpha -dependentregulation of the ABCD2 gene.

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Documento generato il 01/12/20 alle ore 08:04:41