Algal Toxin Azaspiracid-1 Induces Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry

Mar Drugs. 2015 Dec 14;13(12):7390-402. doi: 10.3390/md13127072.

Abstract

Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to most cells and cell lines, little is known about its biological target(s). A rat PC12 cell line, commonly used as a model for the peripheral nervous system, was used to study the neurotoxicological effects of azaspiracid-1. Azaspiracid-1 induced differentiation-related morphological changes followed by a latter cell death. The differentiated phenotype showed peripherin-labelled neurite-like processes simultaneously as a specific isoform of peripherin was down-regulated. The precise mechanism behind this down-regulation remains uncertain. However, this study provides new insights into the neurological effects of azaspiracid-1 and into the biological significance of specific isoforms of peripherin.

Keywords: PC12 cells; algal toxin; azaspiracid; intermediate filament; isoform; neurotoxin; peripherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Differentiation / drug effects
  • Down-Regulation / drug effects
  • Marine Toxins / toxicity*
  • Neurons / drug effects*
  • Neurons / pathology
  • PC12 Cells
  • Peripherins / chemistry
  • Peripherins / metabolism*
  • Protein Isoforms
  • Rats
  • Spiro Compounds / toxicity*

Substances

  • Marine Toxins
  • Peripherins
  • Protein Isoforms
  • Spiro Compounds
  • azaspiracid