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 (O-2(.-))-scavenging ability in cultured mammalian cells. Mn(III)TMPyP (<5 mu M) added to culture media relieved growth inhibition and decre ased the inactivation of the O-2(.-)-sensitive enzyme aconitase in cel ls exposed to the O-2(.-)-generating phenazine pyocyanine. Treatment o f cells with Mn(III)TMPyP did not measureably affect cellular O-2(.-) production as revealed by rates of cyanide-resistant respiration with or without added pyocyanine. In contrast, Mn(II/III)TMPyP enhanced O-2 (.-) production in cells when the redox-active naphthoquinone menadion e was present as measured by both increased cyanide-resistant respirat ion rates and aconitase inactivation. In vitro, Mn(II/III)TMPyP cataly zed the oxidation of ascorbate, and menadione enhanced this effect. Mn (III)TMPyP did not protect aconitase when O-2(.-) production was elici ted in mitochondria by antimycin A and the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone. The results support a reductant-O-2 (.-):oxidoreductase mechanism for O-2(.-)-scavenging by Mn(II/III)TMPy P in the mammalian cytosol as proposed for its action in Escherichia c oli, but also indicate that Mn(II/III)TMPyP can either scavenge or pro duce O-2(.-) in cells depending upon the prevailing pathways of Mn(II/ III)TMPyP oxidation-reduction. (C) 1996 Academic Press, Inc.