Antioxidant cytochrome c-like activity of para-Mn^(III)TMPyP

Manganese porphyrins are well-known protectors against the deleterious effects of pro-oxidant species such as superoxide ions and hydrogen peroxide. The present study investigated the antioxidant cytochrome c-like activities of Mn(III)TMPyP [meso-tetrakis (4-N-methyl pyridinium) porphyrin] against superoxide ion and hydrogen peroxide that remained unexplored for this porphyrin. The association of TMPyP with a model of the inner mitochondrial membrane, cardiolipin (CL)-containing liposomes, shifted +30 mV vs. NHE (normal hydrogen electrode) redox potential of the Mn^(II)/Mn^(III) redox couple. In CL-containing liposomes, Mn^(III)TMPyP was reduced by superoxide ions and recycled by Fe^(III)cytochrome c to the oxidized form. Similarly, isolated rat liver mitoplasts added to a sample of Mn^(II)TMPyP promoted immediate porphyrin reoxidation by electron transfer to the respiratory chain. These results show that Mn^(III)TMPyP can act as an additional pool of Fe^(III)cytochrome c capable of transferring electrons that escape from the IV complex back into the respiratory chain. Unlike Fe^(II)cytochrome c, Mn^(II)TMPyP was not efficient for hydrogen peroxide clearance. Therefore, by reducing cytochrome c, Mn^(II)TMPyP can indirectly contribute to hydrogen peroxide elimination.