Overproduction of human Cu/Zn-superoxide dismutase in transfected cells: extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation.
The 'housekeeping' enzyme Cu/Zn-superoxide dismutase (SOD-1) is encoded by a gene residing on human chromosome 21, at the region 21q22 known to be involved in Down's syndrome. The SOD-1 gene and the SOD-1 cDNA were introduced into mouse L-cells and human HeLa cells, respectively as part of recombinant plasmids containing the neoR selectable marker. Human and mouse transformants were obtained that expressed elevated levels (up to 6-fold) of authentic, enzymatically active human SOD-1. This enabled us to examine the consequences of hSOD-1 gene dosage, apart from gene dosage effects contributed by other genes residing on chromosome 21. Human and mouse cell clones that overproduce the hSOD-1 had altered properties; they were more resistant to paraquat than the parental cells and showed an increase in lipid peroxidation. The data are consistent with the possibility that gene dosage of hSOD-1 contributes to some of the clinical symptoms associated with Down's syndrome.
D000818:Animals; D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004262:DNA Restriction Enzymes; D005796:Genes / Q000187:drug effects; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D007739:L Cells / Q000201:enzymology; D008054:Lipid Peroxides / Q000378:metabolism*; D051379:Mice; D010269:Paraquat / Q000633:toxicity*; D010957:Plasmids; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D008054:Lipid Peroxides; D004247:DNA; D013482:Superoxide Dismutase; D004262:DNA Restriction Enzymes; D010269:Paraquat