Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome.
Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome.
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DOI：
10.1016/j.freeradbiomed.2014.04.002
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发表时间：
2014-07
影响因子：
7.4
通讯作者：
Borg, K.
中科院分区：
文献类型：
--
作者：
Manevich, Y.;Hutchens, S.;Halushka, P. V.;Tew, K. D.;Townsend, D. M.;Jauch, E. C.;Borg, K.
关键词：
创伤性脑损伤（TBI）患者将受益于可靠的生物标志物的识别，以预测预后和治疗策略。在我们的研究中，我们对重症脑外伤患者的脑脊液（CSF）在住院和随后的脑室造瘘安置后的氧化应激介导的损伤进展进行了评估。有趣的是，在对照组和TBI患者的脑脊液中检测到大量水平的过氧化物还蛋白VI (Prdx6)，这是一种通常在星形胶质细胞中发现的主要抗氧化酶，与血液污染无关。在功能上，Prdx6及其相关的结合伙伴谷胱甘肽s -转移酶pi （GSTP1-1，也在脑脊液中检测到）协同作用，以解毒脂质过氧化损伤膜。我们发现Prdx6在对照患者的脑脊液中完全活跃，但在TBI后显着失活（氧化）。此外，与非创伤对照组相比，在入院后24小时内，TBI患者脑脊液中“埋藏”的蛋白硫醇被检测到显著的进行性氧化，氧化程度的增加与创伤的严重程度相关。相反，24小时后Prdx6活性的恢复表明患者预后较好。这不仅是Prdx6细胞外形式的首次报道，也是其在CSF中大量检测到的首次报道。综上所述，我们的数据表明，tbi引发的Prdx6氧化及其特异性磷脂过氧化过氧化物酶活性与创伤结果的严重程度之间存在有意义的相关性。因此，我们提出Prdx6氧化还原状态检测有可能成为TBI结果的生物标志物和未来治疗效果的指标。
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) under TBI. Furthermore, significant and progressive oxidation of “buried” protein thiol in CSF of TBI patients (as compared to that of non-trauma control) were detected over a 24h period following 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.
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影响因子：
7.4
作者：
Manevich, Y.;Hutchens, S.;Tew, K. D.;Townsend, D. M.
通讯作者：
Townsend, D. M.
影响因子：
5.5
作者：
Basuroy, Shyamali;Bhattacharya, Sujoy;Parfenova, Helena
通讯作者：
Parfenova, Helena
影响因子：
4.8
作者：
Bienert, Gerd P.;Moller, Anders L. B.;Jahn, Thomas P.
通讯作者：
Jahn, Thomas P.
影响因子：
9.8
作者：
Goetzl, Laura;Manevich, Yefim;Townsend, Danyelle M.
通讯作者：
Townsend, Danyelle M.
影响因子：
3.7
作者：
Esposito A;Tiffert T;Mauritz JM;Schlachter S;Bannister LH;Kaminski CF;Lew VL
通讯作者：
Lew VL