THE EFFECTS OF UNSATURATED FATTY-ACIDS, OXIDIZING-AGENTS AND MICHAEL REACTION ACCEPTORS ON THE INDUCTION OF N-ETHYLMALEIMIDE REDUCTASE IN ESCHERICHIA-COLI - POSSIBLE APPLICATION FOR DRUG DESIGN OF CHEMOPROTECTORS

Menadione and dimethyl maleate, Michael reaction acceptors, induced N- ethylmaleimide (NEM) reductase activity in Escherichia coli strain DH5 a. Linoleic acid also induced NEM reductase activity, but oleic acid, which is less susceptible to lipid peroxidation than linoleic acid, di d not induce NEM reductase activity. In addition, NEM reductase activi ty was induced by menadione and linoleic acid also in strain DH5, Y108 8 and Y1090. Linoleic acid is not a Michael reaction acceptor, but is known to produce Michael reaction acceptors such as alkenals and 4-hyd roxyalkenals as a result of free-radical-initiated lipid peroxidation. Thus, our findings suggested that lipid peroxidation was involved in the induction of NEM reductase by linoleic acid. The electrophilic pro perty of Michael reaction acceptors provides the signal for induction of phase II enzymes such as glutathione S-transferase and quinone redu ctase in mammals. The inducer potency of phase II enzymes has been use d to design chemoprotective drugs. Therefore, the inducible nature of this enzyme will serve not only for the elucidation of its physiologic al function, but also for the evaluation of chemoprotective drugs.