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Cited by 76Antioxidant Activity and Oxidative StressRedox biology and oxidative stressFree Radicals and Antioxidants

Lipid Peroxyl Radicals Mediate Tyrosine Dimerization and Nitration in Membranes

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Bartesaghi, Silvina, Wenzel, Jorge, Trujillo, Madia, López, Marcos, Joseph, Joy, Kalyanaraman, Balaraman, Radi, Rafael·2010·Chemical Research in Toxicology
DOI 10.1021/tx900446rPMC PMC3506709
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Abstract

Protein tyrosine dimerization and nitration by biologically relevant oxidants usually depend on the intermediate formation of tyrosyl radical ((*)Tyr). In the case of tyrosine oxidation in proteins associated with hydrophobic biocompartments, the participation of unsaturated fatty acids in the process must be considered since they typically constitute preferential targets for the initial oxidative attack. Thus, we postulate that lipid-derived radicals mediate the one-electron oxidation of tyrosine to (*)Tyr, which can afterward react with another (*)Tyr or with nitrogen dioxide ((*)NO(2)) to yield 3,3'-dityrosine or 3-nitrotyrosine within the hydrophobic structure, respectively. To test this hypothesis, we have studied tyrosine oxidation in saturated and unsaturated fatty acid-containing phosphatidylcholine (PC) liposomes with an incorporated hydrophobic tyrosine analogue BTBE (N-t-BOC l-tyrosine tert-butyl ester) and its relationship with lipid peroxidation promoted by three oxidation systems, namely, peroxynitrite, hemin, and 2,2'-azobis (2-amidinopropane) hydrochloride. In all cases, significant tyrosine (BTBE) oxidation was seen in unsaturated PC liposomes, in a way that was largely decreased at low oxygen concentrations. Tyrosine oxidation levels paralleled those of lipid peroxidation (i.e., malondialdehyde and lipid hydroperoxides), lipid-derived radicals and BTBE phenoxyl radicals were simultaneously detected by electron spin resonance spin trapping, supporting an association between the two processes. Indeed, alpha-tocopherol, a known reactant with lipid peroxyl radicals (LOO(*)), inhibited both tyrosine oxidation and lipid peroxidation induced by all three oxidation systems. Moreover, oxidant-stimulated liposomal oxygen consumption was dose dependently inhibited by BTBE but not by its phenylalanine analogue, BPBE (N-t-BOC l-phenylalanine tert-butyl ester), providing direct evidence for the reaction between LOO(*) and the phenol moiety in BTBE, with an estimated second-order rate constant of 4.8 x 10(3) M(-1) s(-1). In summary, the data presented herein demonstrate that LOO(*) mediates tyrosine oxidation processes in hydrophobic biocompartments and provide a new mechanistic insight to understand protein oxidation and nitration in lipoproteins and biomembranes.

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Authors
Bartesaghi, S., Wenzel, J., Trujillo, M., López, M., Joseph, J., Kalyanaraman, B., & Radi, R.
Affiliations
  • Universidad de la República de Uruguay (UY)
  • Departamento de Histología y Embriología, Departamento de Bioquímica, and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Avda. General Flores 2125, 11800 Montevideo, Uruguay, and Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226
ORCID
Venue
Chemical Research in Toxicology
Publisher
American Chemical Society (ACS)
Published
2010-02-19
Volume
23
Issue
4
Pages
821-835
ISSN
  • 0893-228X (ISSN-L)
  • 1520-5010
DOI
10.1021/tx900446r
PMC
PMC3506709
OpenAlex
W2053725496
Cited by
76
References
7
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 9 · 2014: 8 · 2013: 5 · 2012: 11
FWCI
5.12
Type
journal article
Language
en
Open access
Locations
  • Chemical Research in Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Heart, Lung, and Blood Institute (R01HL063119)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
Keywords
lipid peroxyl radicals, tyrosine oxidation, tyrosine nitration, nitrotyrosine, tyrosyl radical, unsaturated fatty acids, phosphatidylcholine liposomes, lipid peroxidation, peroxynitrite, hemin, azo initiators, alpha-tocopherol, oxygen consumption
MeSH terms
Electron Spin Resonance Spectroscopy, Hemin, Lipid Bilayers, Nitrogen Dioxide, Oxidation-Reduction, Peroxides, Tyrosine, Lipid Peroxidation, alpha-Tocopherol, Peroxynitrous Acid, Protein Multimerization

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