0000000000132188
AUTHOR
Stéphane Fourcade
Dehydroepiandrosterone Induction of the Abcd2 and Abcd3 Genes encoding peroxisomal ABC Transporters
Dehydroepiandrosterone (DHEA) is a peroxisome proliferator known to increase the expression of the genes encoding the peroxisomal s-oxidation enzymes in rodents. Using RT-PCR, we analysed the expression of the Abcd2 and Abcd3 genes encoding the peroxisomal ABC transporters ALDRP (ALD related protein) and PMP70 (70 kDa peroxisomal membrane protein) in primary cultures of rats hepatocytes treated with sulfated DHEA. We observed a time (12-72h) and dose (125-500μM) dependent increase in the expression of both genes.
Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2)
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 these partially 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 e…
Thyroid hormone induction of the adrenoleukodystrophy-related gene (ABCD2).
X-linked adrenoleukodystrophy (X-ALD) is a demyelinating disorder associated with impaired very-long-chain fatty-acid (VLCFA) beta-oxidation caused by mutations in the ABCD1 (ALD) gene that encodes a peroxisomal membrane ABC transporter. ABCD2 (ALDR) displays partial functional redundancy because when overexpressed, it is able to correct the X-ALD biochemical phenotype. The ABCD2 promoter contains a putative thyroid hormone-response element conserved in rodents and humans. In this report, we demonstrate that the element is capable of binding retinoid X receptor and 3,5,3'-tri-iodothyronine (T3) receptor (TRbeta) as a heterodimer and mediating T3 responsiveness of ABCD2 in its promoter conte…
Pharmacological Induction of Redundant Genes for a Therapy of X-ALD
X-linked adrenoleukodystrophy (X-ALD) is a recessive neurologic disease with an incidence among males of 1/17 000. Since the identification of the X-ALD gene (ABCD1) ten years ago (Mosser et al 1993), no satisfactory therapy has been available. A close homologue (ABCD2) was then cloned and presented as a putative modifier gene that could account for some of the extreme phenotypic variability of X-ALD (Lombard-Platet et al 1996). The inducibility of Abcd2 by the hypolipidemic drug fenofibrate in the liver of rodents (Albet et al 1997), correlated to a partial normalisation of the biochemical phenotype of X-ALD (Netik et al 1999), opened up the way of a pharmacological therapy of X-ALD. The b…