Recombinant human metallothionein-III alleviates oxidative damage induced by copper and cadmium in Caenorhabditis elegans.

ABSTRACT

Recombinant human metallothionein III (rh-MT-III) is a genetically engineered product produced by Escherichia coli fermentation technology. Its molecules contain abundant reducing sulfhydryl groups, which possess the ability to bind heavy metal ions. The present study was to evaluate the binding effects of rh-MT-III against copper and cadmium in vitro and to investigate the antioxidant activity of rh-MT-III using Caenorhabditis elegans in vivo. For in vitro experiments, the binding rates of copper and cadmium were 91.4% and 97.3% for rh-MT-III at a dosage of 200 µg/mL at 10 h, respectively. For in vivo assays, the oxidative stress induced by copper (CuSO4 , 10 µg/mL) and cadmium (CdCl2 , 10 µg/mL) was significantly reduced after 72 h of exposure to different doses of rh-MT-III (5-500 µg/mL), indicated by restoring locomotion behavior and growth, and reducing malondialdehyde and reactive oxygen species levels in C. elegans. Moreover, rh-MT-III decreased the deposition of lipofuscin and fat content, which could delay the progression of aging. In addition, rh-MT-III (500 µg/mL) promoted the up-regulation of Mtl-1 and Mtl-2 gene expression in C. elegans, which could enhance the resistance to oxidative stress by increasing the enzymatic activity of antioxidant defense system and scavenging free radicals. The results indicated that supplemental rh-MT-III could effectively protect C. elegans from heavy metal stress, providing an experimental basis for the future application and development of rh-MT-III.