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 (O2.-)-scavenging ability in cultured mammalian cells. Mn(III)TMPyP (< 5 microM) added to culture media relieved growth inhibition and decreased the inactivation of the O2(.-)-sensitive enzyme aconitase in cells exposed to the O2(.-)-generating phenazine pyocyanine. Treatment of cells with Mn(III)TMPyP did not measurably affect cellular O2.- production as revealed by rates of cyanide-resistant respiration with or without added pyocyanine. In contrast, Mn(II/III)TMPyP enhanced O2.- 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 O2.- production was elicited in mitochondria by antimycin A and the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone. The results support a reductant-O2.-:oxidoreductase mechanism for O2.- scavenging by Mn(II/III)TMPyP in the mammalian cytosol as proposed for its action in Escherichia coli, but also indicate that Mn(II/III)TMPyP can either scavenge or produce O2.- in cells depending upon the prevailing pathways of Mn(II/III)TMPyP oxidation-reduction.
Gardner
P R
PR
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Nguyen
D D
DD
White
C W
CW
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D003470:Culture Media; D003593:Cytoplasm / Q000378:metabolism; D016166:Free Radical Scavengers; D006801:Humans; D008665:Metalloporphyrins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011710:Pyocyanine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014812:Vitamin K / Q000494:pharmacology
D003470:Culture Media; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D013481:Superoxides; D014812:Vitamin K; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D011710:Pyocyanine; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase; D001205:Ascorbic Acid