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 oxidati on of dihydrorhodamine-123 by peroxynitrite, but does not scavenge nit ric oxide (NO). MnTBAP protects against the suppression of mitochondri al respiration in J774 cells exposed to peroxynitrite or to NO donors. MnTBAP and N-G-methyl-L-arginine provide additive protective effect a gainst the suppression of respiration in immunostimulated cells. Our d ata suggest separate contributions of KO and peroxynitrite to the supp ression of mitochondrial respiration and support the role of oxidative stress in the expression of the inducible isoform of NO synthase.