ENDOGENOUSLY PRODUCED PEROXYNITRITE INDUCES THE OXIDATION OF MITOCHONDRIAL AND NUCLEAR PROTEINS IN IMMUNOSTIMULATED MACROPHAGES

Here we investigated the role of endogenous nitric oxide (NO) and pero xynitrite in the process of protein oxidation (as measured by the dete ction of 2,4-dinitrophenylhydrazine-reactive carbonyls) in immunostimu lated macrophages. Immunostimulation of the macrophages by bacterial l ipopolysaccharide and gamma-interferon (LPS/IFN gamma) resulted in a m arked increase in the oxidation of a large number of mitochondrial and nuclear proteins. The inhibitor of NO synthase, N-G-methyl-L-arginine (3 mM), and the cell-permeable superoxide dismutase mimetic Mn(III)te trakis(4-benzoic acid)porphyrin (300 mu M) both reduced the extent of protein oxidation in response to LPS/IFN gamma. These results support the view that endogenously produced peroxqnitrite induces protein oxid ation in the mitochondria and nucleus of immunostimulated macrophages. (C) 1997 Federation of European Biochemical Societies.