Astrocyte cultures from transgenic mice to study the role of metallothionein in cytotoxicity of tert-butyl hydroperoxide.
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.
Suzuki
Y
Y
Department of Pathology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Apostolova
M D
MD
Cherian
M G
MG
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000032:analysis; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008668:Metallothionein / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015032:Zinc / Q000032:analysis; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D003300:Copper; D008668:Metallothionein; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D015032:Zinc