title: Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome.
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.
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: manevich@musc.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Manevich
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hutchens
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Halushka
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Tew
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Townsend
authors.affiliation: Division of Emergency Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Jauch
authors.affiliation: Division of Pediatric Emergency Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: K
authors.initials: K
authors.lastname: Borg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D054465:Peroxiredoxin VI / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI
keywords: Antioxidant protection; CSF; Choroid plexus; Ependymal cells; Epithelial cells; Free radicals; GSH; Lipid peroxidation; Oxidant stress; Peroxiredoxin VI; Protein thiol; Traumatic brain injury
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