Induction of manganese-superoxide dismutase by membrane-binding drugs in Escherichia coli

Abstract

Treatment of exponentially growing cells of Escherichia coli with membrane-binding drugs such as chlorpromazine (CPZ) and procaine resulted in an induction of manganese-superoxide dismutase (Mn-SOD). A slight decrease was observed in the amount of Fe-SOD. The induction of Mn-SOD required de novo synthesis of this enzyme, since it was suppressed by rifampin. The treatment did not cause the induction of Mn-SOD when performed under anaerobic conditions. In E. coli cells with a sodA-lacZ operon fusion, CPZ and procaine induced beta-galactosidase in the presence of oxygen, whereas it was not expressed and was not induced by CPZ and procaine under anaerobic conditions. Although CPZ reduced the ability of cell suspensions to take up oxygen, it increased the cyanide-resistant fraction of the total respiration. Therefore, it appeared likely that the induction of the sodA gene was a response to an increase in superoxide radical production mediated by these membrane-binding drugs in E. coli cells, possibly by disruption of the electron transport systems in the cell membranes.