RESUMO
The mechanism of an antioxidant action of water-soluble polyol - methanofullerenes C60[C9H10O4(OH)4]6 and C60[C13H18O4(OH)4]6 as the mild uncouplers of an oxidative phosphorylation and respiration is postulated. According to this mechanism, hydroxyl group of methanofullerenols can be protonated under excess of protons in the intermembrane space of hyperpolarized mitochondria. Protonation of fullerene derivatives is confirmed by the decrease in their negative Zeta potential in the pH below 5.4. Heavily protonated methanofullerenols become positively charged and move into the mitochondrial matrix. As a consequence, the proton gradient is dissipated, which causes a decrease in mitochondrial transmembrane potential (ΔΨm) and reduction in ROS production.
Assuntos
Antioxidantes/farmacologia , Fulerenos/farmacologia , Mitocôndrias/efeitos dos fármacos , Polímeros/farmacologia , Antioxidantes/química , Relação Dose-Resposta a Droga , Fulerenos/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Polímeros/química , Solubilidade , Relação Estrutura-Atividade , Água/químicaRESUMO
Here, we report for the first time on two novel water-soluble polyol-methanofullerenes which uncouple respiration and oxidative phosphorylation. A cytofluorimetric JC-1-based ratiometric assay was used to quantify mitochondrial potential Ψm in Yarrowia lipolytica cells exposed to the fullerenes tested. Both methanofullerenes significantly downregulated Ψm, thereby decreasing the subset of cells with high mitochondrial potential compared with intact control cells. The Ψm-low subset of Yarrowia lipolytica cells resulted from methanofullerenes exposure preserved physiological cell size and granularity patterns.
