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Suntres ZE, Lui EM: Prooxidative effect of copper--metallothionein in the acute cytotoxicity of hydrogen peroxide in Ehrlich ascites tumour cells. Toxicology. 2006 Jan 16;217(2-3):155-68. Epub 2005 Oct 10.
This study was concerned with the role of copper (Cu) and Cu-metallothionein (Cu-MT) in oxidative stress. Hydrogen peroxide (H (2) O (2))-induced oxidative injury was examined in Ehrlich ascites tumour cells isolated from host mice pretreated with 0, 1 or 2mg of CuSO (4) (ip) 24h earlier. Control Ehrlich cells contained low levels of Cu and Cu treatment produced dose-related increases in cellular Cu and Cu-MT levels and corresponding increases in sensitivity to oxidative toxicity of H (2) O (2) (LC (50), cell blebbing, lipid peroxidation, GSH depletion, and increase in intracellular free [Ca (2+)](i)). Hydrogen peroxide treatment also resulted in the oxidation of MT thiolates, reduction in the binding of Cu to MT resulting in translocation of Cu to other subcellular sites. d-penicillamine, a Cu-chelating agent, obliterated the sensitization effect of Cu-pretreatment and reduced the redistribution of MT-bound Cu, suggesting the participation of Cu ions derived from MT in promoting oxidant stress. Additional experiments with desferoxamine and mannitol have revealed the involvement of a Cu-dependent Fenton reaction in the mediation of the prooxidative effect of Cu-MT. These data suggest that cells with high levels of Cu-MT may be particularly susceptible to oxidative stress. |
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