Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome |
| |
| Affiliation: | 1. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA;2. Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA;3. Division of Emergency Medicine, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA;4. Division of Pediatric Emergency Medicine, Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA;1. Department of Applied Chemistry and Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 812-8581, Japan;2. Department of Chemistry and Biochemistry, Texas Christian University, Fort Worth, TX 76129, USA;3. Underwood International College, Integrated Science and Engineering Division, Yonsei University, Seoul, 03722, Republic of Korea;1. Children’s Hospital Colorado, 13123 East 16th Avenue, Aurora, CO 80045, USA;2. Department of Neurosurgery, Columbia University Medical Center, New York, NY 10032, USA;3. Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;1. Department of Neurology, Mikkeli Central Hospital, Mikkeli, Finland;2. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland;3. Neuro Center, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland;4. Heart Center Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland;1. Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea;2. Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;1. Division of Applied Molecular Hepatology, Clinics and Policlinics of Visceral, Transplantation, Thoracic, and Vascular Surgery, University of Leipzig, Leipzig, Germany;2. Endocrine Research Unit, Department of Internal Medicine IV, Ludwig Maximilian University, Munich, Germany;3. Department of Pediatrics I, Martin Luther University Halle-Wittenberg, Halle, Germany;1. Vanderbilt University Medical Center, Nashville, Tennessee;2. Vanderbilt Heart and Vascular Institute, Nashville, Tennessee |
| |
| 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 24 h 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. |
| |
| Keywords: | Peroxiredoxin VI Traumatic brain injury CSF Oxidant stress Protein thiol GSH Lipid peroxidation Choroid plexus Epithelial cells Ependymal cells Antioxidant protection Free radicals |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
