Document Detail


Peroxynitrite flux-mediated LDL oxidation is inhibited by manganese porphyrins in the presence of uric acid.
MedLine Citation:
PMID:  14607528     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have studied the role of three Mn(III)porphyrins differing in charge, alkyl substituent length and reactivity, on LDL exposed to low fluxes of peroxynitrite (PN) in the presence of uric acid. Mn(III)porphyrins (5 microM, MnTE-2-PyP(5+), MnTnOct-2-PyP(5+), and MnTCPP(3-)) plus uric acid (300 microM) inhibited cholesteryl ester hydroperoxide formation, changes in REM as well as spared alpha- and gamma-tocopherol. MnTnOct-2-PyP(5+), the more lipophilic compound, was the most effective in protecting LDL lipids, while MnTCPP(3-) exerted the lesser protection. Mn(III)porphyrins react fast with PN ( approximately 10(5)-10(7) M(-1) s(-1)) to yield a O=Mn(IV) complex. The stoichiometry of uric acid consumption was approximately 1.7 moles per mol of PN, in agreement with reactions with both the O=Mn(IV) complex and nitrogen dioxide. A shift from an anti- to a pro-oxidant action of the Mn(III)porphyrin was observed after uric acid was significantly consumed, supporting competition reactions between LDL targets and uric acid for the O=Mn(IV) complex. Overall, the data is consistent with the catalytic reduction of PN in a cycle that involves a one electron oxidation of Mn(III) to Mn(IV) by PN followed by the reduction back to Mn(III) by uric acid. These antioxidant effects should predominate under in vivo conditions having plasma uric acid concentration range between 150 and 500 microM.
Authors:
Andrés Trostchansky; Gerardo Ferrer-Sueta; Carlos Batthyány; Horacio Botti; Ines Batinić-Haberle; Rafael Radi; Homero Rubbo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  35     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-10     Completed Date:  2004-07-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1293-300     Citation Subset:  IM    
Affiliation:
Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
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MeSH Terms
Descriptor/Qualifier:
Humans
Hydrogen Peroxide / metabolism
Lipoproteins, LDL / chemistry*
Manganese / metabolism*
Metalloporphyrins / chemistry,  metabolism*,  pharmacology
Nitrogen Dioxide / metabolism
Oxidation-Reduction*
Peroxynitrous Acid / pharmacology*
Uric Acid / metabolism*
alpha-Tocopherol / metabolism
gamma-Tocopherol / metabolism
Chemical
Reg. No./Substance:
0/Lipoproteins, LDL; 0/Metalloporphyrins; 0/gamma-Tocopherol; 10102-44-0/Nitrogen Dioxide; 14691-52-2/Peroxynitrous Acid; 15213-43-1/manganese(III) porphyrin; 59-02-9/alpha-Tocopherol; 69-93-2/Uric Acid; 7439-96-5/Manganese; 7722-84-1/Hydrogen Peroxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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