6-Hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation

Iron was released from ferritin by the catecholamine analog, 6-hydroxydopamine. Iron release was more efficient under nitrogen than in air, suggesting that the hydroquinone has the major role in the process. Superoxide dismutase, alone or in combination with catalase, strongly inhibited 6-hydroxydopamine oxidation and greatly enhanced the amount of ferritin iron release. Catalase alone had a similar, but lesser effect. Iron released from ferritin accelerated the autoxidation of 6-hydroxydopamine. This occurred by a mechanism that was inhibited by a combination of catalase and a chelator, and to a lesser extent by superoxide dismutase. 6-Hydroxydopamine was a good promoter of metal-catalysed lipid peroxidation, and ferritin-iron participated in the process. Superoxide dismutase, and to a lesser extent catalase, stimulated peroxidation catalysed by adventitious levels of iron, but in the presence of ferritin, each enzyme was inhibitory. It appears that the greatly enhanced iron release seen under these conditions accelerated the autoxidation of 6-hydroxydopamine so that less was available to participate in peroxidative reactions. However, when 6-hydroxydopamine autoxidation was prevented by a combination of superoxide dismutase and catalase, lipid peroxidation was also inhibited, suggesting that some intermediate of autoxidation is a further requirement for the process.