Dehydroepiandrosterone up-regulates the Adrenoleukodystrophy-related gene (ABCD2) independently of PPARα in rodents

摘要: X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by mutations in the ABCD1 gene, which encodes peroxisomal ABC transporter, ALDP, supposed to participate transport of very long chain fatty acids (VLCFA). The adrenoleukodystrophy-related protein (ALDRP), encoded ABCD2 closest homolog ALDP and considered as potential therapeutic target since functional redundancy has been demonstrated between two proteins. Pharmacological induction Abcd2 fibrates through activation PPARalpha rodent liver. DHEA, most abundant steroid human, described activator also prohormone able mediate several genes. Here, we explored vitro vivo effects DHEA on expression transporters. We show that Abcd3 but not Abcd4 are induced primary culture rat hepatocytes DHEA-S. demonstrate inducible an 11-day treatment with liver male rodents brain, testes adrenals. Finally contrary Abcd3, mechanism independent PPARalpha.