Evaluation of the relative contribution of nitric oxide and peroxynitrite to the suppression of mitochondrial respiration in immunostimulated macrophages using a manganese mesoporphyrin superoxide dismutase mimetic and peroxynitrite scavenger.
Here we report that the cell-permeable superoxide dismutase mimetic Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP) inhibits the oxidation of dihydrorhodamine-123 by peroxynitrite, but does not scavenge nitric oxide (NO). MnTBAP protects against the suppression of mitochondrial respiration in J774 cells exposed to peroxynitrite or to NO donors. MnTBAP and N(G)-methyl-L-arginine provide additive protective effect against the suppression of respiration in immunostimulated cells. Our data suggest separate contributions of NO and peroxynitrite to the suppression of mitochondrial respiration and support the role of oxidative stress in the expression of the inducible isoform of NO synthase.
Szabó
C
C
Children's Hospital Medical Center, Division of Critical Care, Cincinnati, OH 45229, USA.
Day
B J
BJ
Salzman
A L
AL
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D004048:Diethylamines / Q000494:pharmacology; D004926:Escherichia coli; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008345:Manganese / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D014664:Vasodilation; D019323:omega-N-Methylarginine
D004048:Diethylamines; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D009566:Nitrates; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; C039642:peroxynitric acid; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D008345:Manganese; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; C034281:diethylamine; D013482:Superoxide Dismutase; D010396:Penicillamine