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 H2O2, 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 H2O2-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.
