Brevetoxin-6 (PbTx-6), a nonaromatic marine neurotoxin, is a ligand of the aryl hydrocarbon receptor

B. S. Washburn, K. S. Rein, D. G. Baden, P. J. Walsh, D. E. Hinton, K. Tullis, M. S. Denison

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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 CY1PA1 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.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume343
Issue number2
DOIs
StatePublished - Jul 15 1997

Keywords

  • Ah receptor
  • Brevetoxin
  • Cytochrome P4501A1
  • EROD
  • Marine toxins
  • Natural toxins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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    Washburn, B. S., Rein, K. S., Baden, D. G., Walsh, P. J., Hinton, D. E., Tullis, K., & Denison, M. S. (1997). Brevetoxin-6 (PbTx-6), a nonaromatic marine neurotoxin, is a ligand of the aryl hydrocarbon receptor. Archives of Biochemistry and Biophysics, 343(2), 149-156. https://doi.org/10.1006/abbi.1997.0149