Role of copper,zinc-superoxide dismutase in catalyzing nitrotyrosine formation in murine liver.
The only known function of Cu,Zn-superoxide dismutase (SOD1) is to catalyze the dismutation of superoxide anion into hydrogen peroxide. Our objective was to determine if SOD1 catalyzes murine liver protein nitration induced by acetaminophen (APAP) and lipopolysaccharide (LPS). Liver and plasma samples were collected from young adult SOD1 knockout mice (SOD1-/-) and wild-type (WT) mice at 5 or 6 h after an ip injection of saline, APAP, or LPS. Hepatic nitrotyrosine formation was induced by APAP and LPS only in the WT mice. The diminished hepatic protein nitration in the SOD1-/- mice was not directly related to plasma nitrite and nitrate concentrations. Similar genotype differences were seen in liver homogenates treated with a bolus of peroxynitrite. Adding only the holo-, and not the apo-, SOD1 enzyme into the liver homogenates enhanced the reaction in an activity-dependent fashion and nearly eliminated the genotype difference at the high doses. Mass spectrometry showed four more nitrotyrosine residues in bovine serum albumin and 10 more nitrated protein candidates in the SOD1-/- liver homogenates by peroxynitrite with added SOD1. In conclusion, the diminished hepatic protein nitration mediated by APAP or LPS in the SOD1-/- mice is due to the lack of SOD1 activity per se.
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
Jian-Hong
JH
Zhu
Xiaomei
X
Zhang
Carol A
CA
Roneker
James P
JP
McClung
Sheng
S
Zhang
Theodore W
TW
Thannhauser
Daniel R
DR
Ripoll
Qi
Q
Sun
Xin Gen
XG
Lei
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D002384:Catalysis; D002417:Cattle; D005838:Genotype; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D009584:Nitrogen / Q000378:metabolism; D009589:Nitrogen Oxides / Q000097:blood; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; C002744:3-nitrotyrosine; D000082:Acetaminophen; D014443:Tyrosine; D013482:Superoxide Dismutase; D009584:Nitrogen