Overexpression of human metallothionein‐III prevents hydrogen peroxide‐induced oxidative stress in human fibroblasts

Metallothioneins (MT) are ubiquitous low molecular weight metal binding proteins that may act as antioxidants. In the present study, the cloned human MT-III coding region was permanently transfected into GM00637 cells in order to investigate the antioxidative effects of this brain-specific MT isoform. GM00637/MT-III cells overexpressed MT-III mRNA versus pcDNA3 plasmid-transfected control cells (GM00637). When challenged with H(2)O(2), the GM00637/MT-III cells displayed significantly more resistance than the GM00637 cells, as determined by cell cytotoxicity, lactate dehydrogenase leakage, and lipid peroxidation. In addition, the GM00637/MT-III cells were highly protected from the H(2)O(2)-induced production of reactive oxygen species and DNA damage. These results directly support the antioxidative role of MT-III, and demonstrate MT-III can scavenge free oxygen radicals and protect cells from oxidative stress.