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Brevetoxin-6 (PbTx-6), a nonaromatic marine neurotoxin, is a ligand of the aryl hydrocarbon receptor.
Washburn, B S; Rein, K S; Baden, D G; Walsh, P J; Hinton, D E; Tullis, K; Denison, M S.
Afiliación
  • Washburn BS; Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Arch Biochem Biophys ; 343(2): 149-56, 1997 Jul 15.
Article en En | MEDLINE | ID: mdl-9224724
Brevetoxins (PbTx) are a family of marine polyether toxins that exert their toxic action by activating voltage-sensitive sodium channels. Two forms of brevetoxin, PbTx-2 and -3, induce hepatic cytochrome P4501A1, measured as ethoxyresorufin O-deethylase (EROD) activity, in redfish and striped bass. P4501A1 induction is transcriptionally regulated through the binding of a ligand, typically a planar aromatic compound, to the aryl hydrocarbon receptor (AhR) and subsequent complex formation with the dioxin response element (DRE), an upstream regulatory region of the CYP1A1 gene. To determine if PbTx, a nonaromatic compound, induced EROD by this mechanism, two sets of experiments were performed. Initially, saturation binding assays with PbTx-2, -3, and -6 were carried out to determine if PbTx-2, -3, or -6 was an AhR ligand. Results showed that PbTx-6 inhibited specific binding of dioxin to the AhR, whereas PbTx-2 and -3 had no effect. Subsequently, gel retardation assays showed that PbTx-6 caused a concentration-dependent increase in AhR-DRE complex formation. The most abundant and neurotoxic forms of brevetoxin, PbTx-2 and -3, did not appear to be involved in this process. However, PbTx-6, the epoxide which is a likely biotransformation product, is at least one of the forms of PbTx involved in EROD induction.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Secuencias Reguladoras de Ácidos Nucleicos / Receptores de Hidrocarburo de Aril / Citocromo P-450 CYP1A1 / Oxocinas / Hígado / Toxinas Marinas / Neurotoxinas Límite: Animals Idioma: En Revista: Arch Biochem Biophys Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Secuencias Reguladoras de Ácidos Nucleicos / Receptores de Hidrocarburo de Aril / Citocromo P-450 CYP1A1 / Oxocinas / Hígado / Toxinas Marinas / Neurotoxinas Límite: Animals Idioma: En Revista: Arch Biochem Biophys Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos