Superoxide Scavenging by Mn(II/III) Tetrakis (1-Methyl-4-pyridyl) Porphyrin in Mammalian Cells

The superoxide dismutase mimic Mn(II/III) tetrakis (1-methyl-4-pyridyl) porphyrin (Mn(II/III)TMPyP) was examined for its superoxide radical[formula]-scavenging ability in cultured mammalian cells. Mn(III)TMPyP (<5 μM) added to culture media relieved growth inhibition and decreased the inactivation of the[formula]-sensitive enzyme aconitase in cells exposed to the[formula]-generating phenazine pyocyanine. Treatment of cells with Mn(III)TMPyP did not measureably affect cellular[formula]production as revealed by rates of cyanide-resistant respiration with or without added pyocyanine. In contrast, Mn(II/III)TMPyP enhanced[formula]production in cells when the redox-active naphthoquinone menadione was present as measured by both increased cyanide-resistant respiration rates and aconitase inactivation.In vitro,Mn(II/III)TMPyP catalyzed the oxidation of ascorbate, and menadione enhanced this effect. Mn(III)TMPyP did not protect aconitase when[formula]production was elicited in mitochondria by antimycin A and the uncoupler carbonyl cyanidep-trifluoromethoxyphenylhydrazone. The results support a reductant-[formula]:oxidoreductase mechanism for[formula]scavenging by Mn(II/III)TMPyP in the mammalian cytosol as proposed for its action inEscherichia coli,but also indicate that Mn(II/III)TMPyP can either scavenge or produce[formula]in cells depending upon the prevailing pathways of Mn(II/III)TMPyP oxidation–reduction.