Characterization of nitrotyrosine-modified proteins in cerebrospinal fluid

Ashley S. Beasley, Caroline Anderson, Justin McArthur, Ned Sacktor, Avindra Nath, Robert J. Cotter

Research output: Contribution to journalArticlepeer-review

Abstract

Background: HIV-associated neurocognitive disorders (HAND) has been associated with the up-regulation of various oxidative stress pathways. Previous studies have linked the neuronal damage observed in individuals diagnosed with HAND to increased nitrotyrosine modification of neuronal proteins. Materials and methods: Tyrosine nitration alters protein structure and function, affects biological half-life, and potentially prevents the phosphorylation of key tyrosine residues involved in signal transduction pathways. Therefore, in this study we employed proteomics-based experimental approaches to investigate nitrotyrosine-modified proteins in pooled cerebrospinal fluid (CSF) of individuals diagnosed with HAND. To identify specific nitrotyrosine-modified proteins in the CSF of individuals diagnosed with HAND, affinity purification and high-performance tandem mass spectrometry are utilized in a "bottom-up" proteomics approach. Results: From tandem mass spectrometric analysis, we identified major proteins that underwent nitration as a result of nitro-oxidative stress in the CSF of individuals diagnosed with HAND. We also utilized analytical and biochemical techniques to characterize the expression and modification site of in vivo nitrated lipocalin-type prostaglandin-D synthase in HAND CSF.

Original languageEnglish (US)
Pages (from-to)29-41
Number of pages13
JournalClinical Proteomics
Volume6
Issue number1-2
DOIs
StatePublished - Jun 2010

Keywords

  • BSA
  • CSF
  • HAND
  • HIV
  • Oxidative stress
  • Tyrosine nitration

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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