MENADIONE INDUCES CHANGES IN THE MEMBRANE ELECTRICAL-PROPERTIES ASSOCIATED WITH DOWN-REGULATION OF INSULIN-RECEPTORS IN HUMAN ERYTHROCYTES

We have demonstrated using dielectric relaxation measurements in the r adiofrequency range that the electrical properties of human erythrocyt es (membrane conductivity and permittivity as well as the conductivity of the cytosol) undergo a steady decrease over time during insulin-in duced downregulation of insulin receptors (Santini et al., Experimenta l Hematology 22:40-44, 1994). In the present paper, we show that expos ure of these erythrocytes to the strong oxidizing agent menadione befo re addition of insulin blocks insulin receptor internalization as well as the decrease in electrical parameters associated with this process . We hypothesize that menadione blocks internalization of these recept ors by inducing oxidative damage on the erythrocytes and, consequently , disrupting the normally occurring variations in electrical parameter s. This postulate was confirmed by addition of the antioxidant N-acety lcysteine to menadione-treated cells, in which a return to the origina l changes in electrical parameters noted in untreated cells was observ ed.