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Free Radic Biol Med. 2014 Jul;72:210-21. doi: 10.1016/j.freeradbiomed.2014.04.002. Epub 2014 Apr 12.

Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome.

Author information

  • 1Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: manevich@musc.edu.
  • 2Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
  • 3Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
  • 4Division of Emergency Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
  • 5Division of Pediatric Emergency Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA.

Abstract

Traumatic brain injury (TBI) patients would benefit from the identification of reliable biomarkers to predict outcomes and treatment strategies. In our study, cerebrospinal fluid (CSF) from patients with severe TBI was evaluated for oxidant stress-mediated damage progression after hospital admission and subsequent ventriculostomy placement. Interestingly, substantial levels of peroxiredoxin VI (Prdx6), a major antioxidant enzyme normally found in astrocytes, were detected in CSF from control and TBI patients and were not associated with blood contamination. Functionally, Prdx6 and its associated binding partner glutathione S-transferase Pi (GSTP1-1, also detected in CSF) act in tandem to detoxify lipid peroxidation damage to membranes. We found Prdx6 was fully active in CSF of control patients but becomes significantly inactivated (oxidized) in TBI. Furthermore, significant and progressive oxidation of "buried" protein thiols in CSF of TBI patients (compared to those of nontrauma controls) was detected over a 24-h period after hospital admission, with increased oxidation correlating with severity of trauma. Conversely, recovery of Prdx6 activity after 24h indicated more favorable patient outcome. Not only is this the first report of an extracellular form of Prdx6 but also the first report of its detection at a substantial level in CSF. Taken together, our data suggest a meaningful correlation between TBI-initiated oxidation of Prdx6, its specific phospholipid hydroperoxide peroxidase activity, and severity of trauma outcome. Consequently, we propose that Prdx6 redox status detection has the potential to be a biomarker for TBI outcome and a future indicator of therapeutic efficacy.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Antioxidant protection; CSF; Choroid plexus; Ependymal cells; Epithelial cells; Free radicals; GSH; Lipid peroxidation; Oxidant stress; Peroxiredoxin VI; Protein thiol; Traumatic brain injury

PMID:
24726861
[PubMed - indexed for MEDLINE]
PMCID:
PMC4088265
Free PMC Article
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