Abstract

Activated human phagocytes employ the myeloperoxidase-H2O2-Cl system to convert L-tyrosine into the amphipathic aldehyde, p-hydroxyphenylacetaldehyde (pHA). We have explored the possibility that pHA covalently reacts with proteins, which may play a role in modifying targets at sites of inflammation. Purified pHA rapidly reacted with A2-acetyllysine, an analog of protein lysine residues. After reductin with NaCNBH3 the reaction product was identified as Na-acetyl-N3-p-hydroxyphenylethyllysine by 1H NMR spectroscopy and mass spectrometry. p-Hydroxyphenylethyllysine (pHA-lysine) was likewise formed on BSA exposed to l-tyrosine and the myeloperoxidase_H2O2-Cl system. Incubation of BSA and L-tyrosine with a variety of in vitro oxidation systems demonstrated that pHA-lysine is a specific marker for protein modification by myeloperoxidase. pHA-Lysine was formed in BSA exposed to activated neutrophils and L-tyrosine. Because pHA-lysine is a specific marker of protein modificat ion by myeloperoxidase, its identification may pinpoint targets where phagocytes inflict oxidative damage in vivo.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-24
Application #
6336774
Study Section
Project Start
2000-08-01
Project End
2001-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
24
Fiscal Year
2000
Total Cost
$6,028
Indirect Cost

  Institution

Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Yue, Xuyi; Dhavale, Dhruva D; Li, Junfeng et al. (2018) Design, synthesis, and in vitro evaluation of quinolinyl analogues for ?-synuclein aggregation. Bioorg Med Chem Lett 28:1011-1019
Ohlemacher, Shannon I; Giblin, Daryl E; d'Avignon, D André et al. (2017) Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 127:4018-4030
Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
Ovod, Vitaliy; Ramsey, Kara N; Mawuenyega, Kwasi G et al. (2017) Amyloid ? concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841-849
Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Wei, Xiaochao; Song, Haowei; Yin, Li et al. (2016) Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 539:294-298
Shields-Cutler, Robin R; Crowley, Jan R; Miller, Connelly D et al. (2016) Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine. J Biol Chem 291:25901-25910
Mertins, Philipp; Mani, D R; Ruggles, Kelly V et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534:55-62
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62

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