Metallothionein protects DNA from oxidative damage

Abstract

Metallothionein (MT) is a potent hydroxyl radical scavenger but its antioxidant properties in vivo have not been defined. Most of the recent results indicate that it does not afford protection to cells against the lethal action of oxidative stress. However, the possibility that MT confers protection against oxidative damage to a specific cellular target, such as DNA, had not been considered. We compared V79 Chinese hamster cells enriched in and depleted of MT in terms of DNA-strand scission. Zinc induces an increase in MT content of V79 Chinese hamster cells, without concomitant increase in the GSH level. These induced cells are more resistant to the production of DNA-strand scission by H2O2 than the parental cells. Conversely, cells rendered partially deprived of MT, by transfection with a plasmid vector in which the MT-I cDNA is antisense oriented in relation to a simian virus 40 promoter, became more susceptible to the DNA-damaging action of H2O2. The transfected cells did not exhibit alterations of GSH, superoxide dismutase- and H2O2-destroying enzymes. Indirect immunofluorescence indicated that most of the MT was concentrated in the cell nucleus. Neither overexpression nor lower expression of MT resulted in differential resistance to the killing action of H2O2. However, the combined high nuclear concentration of MT and its excellent hydroxyl scavenger properties confer protection to DNA from hydroxyl radical attack.

Detoxification mechanisms in shrimp: Comparative approach between hydrothermal vent fields and estuarine environments

“…chacei from LS) may have an antioxidant role in ROS detoxification inside the cells, mainly in the elimination of hydroxyl radical, as described by Chubatsu and Meneghini (1993). Finally, the results suggest that biochemical responses in vent and coastal shrimp are not exclusively affected by environmental characteristics (i.e.…”

Large‐scale identification of leaf senescence‐associated genes

“…The precise role of these two proteins is not clear, but they may have dual roles: detoxi®cation of metal ions released during protein breakdown and/or to function as metal-binding proteins for storage or transport into developing organs (Buchanan-Wollaston and Ainsworth, 1997). Evidence from mammalian cells suggests that metallothioneins protect DNA from damage (Chubatsu and Meneghini, 1993).…”

Induction of metallothionein as an adaptive mechanism affecting the magnitude and progression of toxicological injury.

“…MT can serve as a sacrificial scavenger for hydroxyl radicals in vitro (35) and protect against free radical-induced DNA damage (36)(37)(38). MT can also assume the function of superoxide dismutase in yeast (39) and protect against lipid peroxidation in erythrocyte ghosts produced by xanthine oxidase-derived superoxide anion and hydrogen peroxide (40).…”