Astrocyte cultures from transgenic mice to study the role of metallothionein in cytotoxicity of tert-butyl hydroperoxide

Toxicology. 2000 Apr 7;145(1):51-62. doi: 10.1016/s0300-483x(99)00220-6.


The cell viability, lipid peroxidation (LPO) and hydrogen peroxide (H(2)O(2)) generation were measured in cultured primary astrocytes, from metallothionein (MT)-I isoform overexpressing transgenic (MT-I*), MT-I/MT-II null and control mice after exposure to tert-butylhydroperoxide (tBH). Astrocytes from MT-I* mice have high basal levels of both MT-I mRNA and MT protein, whereas there is only MT-III isoform in astrocytes from MT-I/MT-II null mice. The results showed that (1) cultured astrocytes from MT-I* mice were most resistant to the cytotoxicity of tBH and those from MT-I/MT-II null mice were most sensitive to the cytotoxicity of tBH; (2) LPO after exposure to tBH were increased in all cells, but the levels were the highest in astrocytes from MT-I/MT-II null mice, while those in MT-I* mice were the lowest; (3) the levels of H(2)O(2) in cultured astrocytes from MT-I* mice were the lowest, while those in astrocytes from MT-I/MT-II null mice were the highest. These results support the hypothesis that MT can scavenge free radicals and protect astrocytes from oxidative stress.

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Copper / analysis
  • Hydrogen Peroxide / metabolism
  • Lipid Peroxidation / drug effects
  • Metallothionein / analysis
  • Metallothionein / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Zinc / analysis
  • tert-Butylhydroperoxide / toxicity*


  • Copper
  • Metallothionein
  • tert-Butylhydroperoxide
  • Hydrogen Peroxide
  • Zinc