Menadione induces changes in the membrane electrical properties associated with downregulation of insulin receptors in human erythrocytes.
We have demonstrated using dielectric relaxation measurements in the radiofrequency range that the electrical properties of human erythrocytes (membrane conductivity and permittivity as well as the conductivity of the cytosol) undergo a steady decrease over time during insulin-induced downregulation of insulin receptors (Santini et al., Experimental Hematology 22:40-44, 1994). In the present paper, we show that exposure of these erythrocytes to the strong oxidizing agent menadione before 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 receptors by inducing oxidative damage on the erythrocytes and, consequently, disrupting the normally occurring variations in electrical parameters. This postulate was confirmed by addition of the antioxidant N-acetylcysteine to menadione-treated cells, in which a return to the original changes in electrical parameters noted in untreated cells was observed.
Santini
M T
MT
Laboratorio di Ultrastrutture, Istituto Superiore di Sanità, Rome, Italy.
Cametti
C
C
Indovina
P L
PL
Peterson
S W
SW
D015536:Down-Regulation; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D011972:Receptor, Insulin / Q000096:biosynthesis*
D007328:Insulin; D011972:Receptor, Insulin