Identification of a putative calcium-binding protein as a dioxin-responsive gene in zebrafish and rainbow trout

Aquat Toxicol. 2003 May 8;63(3):271-82. doi: 10.1016/s0166-445x(02)00184-4.


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a widespread environmental contaminant that causes multiple effects in vertebrates. TCDD elicits its toxicity through aryl hydrocarbon receptor (AhR)-mediated modulation of gene regulation, increasing intracellular free calcium, and inducing calcium-mediated apoptosis in cell culture. Two TCDD-responsive cDNAs, which encode putative calcium-binding proteins, have been isolated from zebrafish and rainbow trout. The zebrafish and rainbow trout sequences are 88% similar to each other at the amino acid level and are orthologs of the human S100A4 calcium-binding protein. In zebrafish liver cell culture, treatment with TCDD increases S100A4a mRNA abundance. In juvenile rainbow trout, S100A4 mRNA was constitutively expressed in the heart, kidney, intestine, and spleen, but not in the liver. Exposure to TCDD significantly increased rainbow trout S100A4 mRNA abundance in the rainbow trout kidney. Taken together, these findings demonstrate in zebrafish and rainbow trout that dioxin increases expression of this EF-hand calcium-binding protein gene in a tissue-dependent fashion. However, demonstration that the encoded S100A4 proteins actually bind calcium and play a role in dioxin toxicity will require further study.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Binding Proteins / drug effects
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cells, Cultured
  • Environmental Pollutants / toxicity*
  • Gene Expression / physiology
  • Kidney / metabolism
  • Liver / cytology
  • Liver / metabolism
  • Molecular Sequence Data
  • Oncorhynchus mykiss / genetics*
  • Oncorhynchus mykiss / metabolism
  • Polychlorinated Dibenzodioxins / toxicity*
  • S100 Proteins / drug effects
  • S100 Proteins / genetics
  • S100 Proteins / isolation & purification
  • S100 Proteins / metabolism*
  • Sequence Homology
  • Species Specificity
  • Tissue Distribution
  • Zebrafish / genetics*
  • Zebrafish / metabolism


  • Calcium-Binding Proteins
  • Environmental Pollutants
  • Polychlorinated Dibenzodioxins
  • S100 Proteins