Ubiquinone-0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone) as effective catalyzer of ascorbate and epinephrine oxidation and damager of neuroblastoma cells

The kinetics of ascorbate (AscH(-)) and epinephrine (EP) oxidation in the presence of 2,3-dimethoxy-5-methyl-1,4-benzaquinone (UQ) were studied in 0.05 M phosphate buffer, pH 7.4, at 31 degrees C by using a Clark electrode and ESR techniques. UQ at nanomolar concentrations displayed a pronounced catalytic effect on AscH(-) oxidation which exceeded that of all reported organic catalysts tested in this system. The process was accompanied by the intensive oxygen consumption and increase in the steady-state concentration of the ascorbyl radical Asc(-). The rate of oxygen consumption (R-OX) was maximal at the moment of reagent mixing ((R-OX)(O)) and then reduced over a few minutes until a steady-state level ((R-OX)(SS)) was achieved. (R-OX)(O) was found to be proportional to [UQ][AscH(-)] without regard to the concentrations of the individual reagents; (R-OX)(SS) was directly related to [UQ] at a given concentration of AscH(-). The difference between (R-OX)(O) and (R-OX)(SS) decreased as [AscH(-)] decreased. The presence of a lipid phase (sodium dodecylsulphate micelles) only moderately decreased UR activity as a catalyst of AscH(-) oxidation. Adding micromolar concentrations of UQ induced the acceleration of EP autoxidation. The capability of UQ to catalyze the oxidation of EP exceeded by approximately 25 times that of adrenochrome, a quinoid product of EP oxidation. These catalytic properties of UQ allowed us to predict its pronounced cytotoxicity, especially in the presence of AscH(-) and to cells of the sympathetic nervous system which are rich in catecholamines. This possibility was confirmed by experiments with human neuroblastoma cells in culture. The capability of UQ to injure neuroblastoma cell line SK-N-SH exceeded that of well-known neurotoxic agents 6-hydroxydopamine and menadione. (C) 1998 Elsevier Science Inc.