Diethyldithiocarbamate inhibits in vivo Cu,Zn-superoxide dismutase and perturbs free radical processes in the yeast Saccharomyces cerevisiae cells

• Published in: Biochemical and biophysical research communications Vol. 338; no. 4; pp. 1739 - 1744
• Main Authors: Lushchak, Volodymyr, Semchyshyn, Halyna, Lushchak, Oleh, Mandryk, Serhij
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.12.2005
• Subjects: Antioxidant enzymes; Carbonylproteins; Catalase - metabolism; Cu,Zn-superoxide dismutase; Diethyldithiocarbamate; Ditiocarb - pharmacology; Enzyme Activation; Free Radicals - metabolism; Glucosephosphate Dehydrogenase - metabolism; Glutathione Reductase - metabolism; Isocitrate Dehydrogenase - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - metabolism; Superoxide Dismutase - antagonists & inhibitors; Diethyldithiocarbamate; Carbonylproteins; Cu,Zn-superoxide dismutase; Saccharomyces cerevisiae
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.10.147

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 10 mM 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 ( R 2 = 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.