Abstract:
:Nitration of protein tyrosine residues to 3-nitrotyrosine (NO2Tyr) serves as both a marker and mediator of pathogenic reactions of nitric oxide (*NO), with peroxynitrite (ONOO-) and leukocyte peroxidase-derived nitrogen dioxide (*NO2) being proximal mediators of nitration reactions in vivo. Cytochrome c is a respiratory and apoptotic signaling heme protein localized exofacially on the inner mitochondrial membrane. We report herein a novel function for cytochrome c as a catalyst for nitrite (NO2-) and hydrogen peroxide (H2O2)-mediated nitration reactions. Cytochrome c catalyzes both self- and adjacent-molecule (hydroxyphenylacetic acid, Mn-superoxide dismutase) nitration via heme-dependent mechanisms involving tyrosyl radical and *NO2 production, as for phagocyte peroxidases. Although low molecular weight phenolic nitration yields were similar for cytochrome c and the proteolytic fragment of cytochrome c microperoxidase-11 (MPx-11), greater extents of protein nitration occurred when MPx-11 served as catalyst. Partial proteolysis of cytochrome c increased both the peroxidase and nitrating activities of cytochrome c. Extensive tyrosine nitration of Mn-superoxide dismutase occurred when exposed to either cytochrome c or MPx-11 in the presence of H2O2 and NO2-, with no apparent decrease in catalytic activity. These results reveal a post-translational tyrosine modification mechanism that is mediated by an abundant hemoprotein present in both mitochondrial and cytosolic compartments. The data also infer that the distribution of specific proteins capable of serving as potent catalysts of nitration can lend both spatial and molecular specificity to biomolecule nitration reactions.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Castro L,Eiserich JP,Sweeney S,Radi R,Freeman BAdoi
10.1016/j.abb.2003.08.033subject
Has Abstractpub_date
2004-01-01 00:00:00pages
99-107issue
1eissn
0003-9861issn
1096-0384pii
S0003986103004351journal_volume
421pub_type
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
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journal_title:Archives of biochemistry and biophysics
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更新日期:1995-02-20 00:00:00
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journal_title:Archives of biochemistry and biophysics
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更新日期:1990-11-01 00:00:00