Redox-dependent regulation of intracellular trafficking of the glucocorticoid receptor

Abstract

Ubiquinone (UQ) is the only natural compound which was reported both to generate and to scavenge oxygen-derived radicals. Redox-cycling of ubiquinone may yield six different species of the parent compound: UQH2, UQH−, UQ2−, UQH•, UQ•−, and UQ. Ubiquinol (UQH2) is unequivocally considered to be the ubiquinone species capable of scavenging oxygen-derived radicals. In contrast, the ubiquinone species responsible for one e−reduction of dioxygen (O2) thereby initiating the cascade of oxidative stress is still a matter of controversial debate. In the present study this question was approached by following the effect of O2on the stability of the various reduced forms of UQ. For this purpose conditions were designed allowing the selective accumulation of the two protonated and of the two deprotonated forms of reduced ubiquinones. Our results exclude both protonated (ubiquinol, UQH2) and anionic (ubiquinol anion, UQH−, and ubiquinol dianion, UQ2−) fully reduced ubiquinones as the source exerting one e−reduction of O2. Ubisemiquinone (semiquinone radical, UQH•), when protonated, underwent rapid disproportionation, while transition to the semireduced anionic form (semiquinone radical anion, UQ•−) was found to favor autoxidation. The results obtained in this study provide a chemical base for the assessment of one e−transfer from redox-cycling UQ to O2in the respiratory chain and in biomembranes where ubihydroquinol is suggested to exert antioxidant activities.