Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells

Int J Mol Sci. 2016 Aug 23;17(9):1381. doi: 10.3390/ijms17091381.

Abstract

Vascular endothelial cells cover the luminal surface of blood vessels and contribute to the prevention of vascular disorders such as atherosclerosis. Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, inducible protein, which protects cells from the toxicity of heavy metals and active oxygen species. Endothelial MT is not induced by inorganic zinc. Adequate tools are required to investigate the mechanisms underlying endothelial MT induction. In the present study, we found that an organoantimony compound, tris(pentafluorophenyl)stibane, induces gene expression of MT-1A and MT-2A, which are subisoforms of MT in bovine aortic endothelial cells. The data reveal that MT-1A is induced by activation of both the MTF-1-MRE and Nrf2-ARE pathways, whereas MT-2A expression requires only activation of the MTF-1-MRE pathway. The present data suggest that the original role of MT-1 is to protect cells from heavy metal toxicity and oxidative stress in the biological defense system, while that of MT-2 is to regulate intracellular zinc metabolism.

Keywords: bio-organometallics; metallothionein; organic–inorganic hybrid molecule; organoantimony compound; vascular endothelial cell.

MeSH terms

  • Animals
  • Aorta / cytology*
  • Cattle
  • DNA-Binding Proteins / genetics
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Glutamate-Cysteine Ligase / genetics
  • Heme Oxygenase-1 / genetics
  • Hydrocarbons, Chlorinated / pharmacology*
  • Metallothionein / genetics*
  • NF-E2-Related Factor 2 / genetics
  • Protein Isoforms / genetics
  • Transcription Factor MTF-1
  • Transcription Factors / genetics
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics

Substances

  • DNA-Binding Proteins
  • Hydrocarbons, Chlorinated
  • NF-E2-Related Factor 2
  • Protein Isoforms
  • Transcription Factors
  • Metallothionein
  • Heme Oxygenase-1
  • Glutamate-Cysteine Ligase