Diethyldithiocarbamate inhibits in vivo Cu,Zn-superoxide dismutase and perturbs free radical processes in the yeast Saccharomyces cerevisiae cells.
Copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese superoxide dismutase (Mn-SOD) in some model experiments in vitro demonstrated antioxidant as well as pro-oxidant properties. In the present study, yeast Saccharomyces cerevisiae lacking Mn-SOD were studied using Cu,Zn-SOD inhibitor N-N'-diethyldithiocarbamate (DDC) as a model system to study the physiological role of the yeast Cu,Zn-SOD. Yeast treatment by DDC caused dose-dependent inhibition of SOD in vivo, with 75% inhibition at 10mM DDC. The inhibition of SOD by DDC resulted in modification of carbonylprotein levels, indicated by a bell-shaped curve. The activity of glutathione reductase, isocitrate dehydrogenase, and glucose-6-phosphate dehydrogenase (enzymes associated with antioxidant) increased, demonstrating a compensatory effect in response to SOD inhibition by different concentrations of DDC. A strong positive correlation (R2=0.97) was found between SOD and catalase activities that may be explained by the protective role of SOD for catalase. All observed effects were absent in the isogenic SOD-deficient strain that excluded direct DDC influence. The results are discussed from the point of view that in vivo Cu,Zn-SOD of S. cerevisiae can demonstrate both anti- and pro-oxidant properties.
Lushchak
Volodymyr
V
Department of Biochemistry, Vassyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76025, Ukraine.
Semchyshyn
Halyna
H
Lushchak
Oleh
O
Mandryk
Serhij
S
D002374:Catalase / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology*; D004789:Enzyme Activation; D005609:Free Radicals / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*
D005609:Free Radicals; D004050:Ditiocarb; D007521:Isocitrate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase