DIFFERENTIAL CELLULAR LOCALIZATION OF ANTIOXIDANT ENZYMES IN THE TRIGEMINAL GANGLION
DIFFERENTIAL CELLULAR LOCALIZATION OF ANTIOXIDANT ENZYMES IN THE TRIGEMINAL GANGLION
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DOI：
10.1016/j.neuroscience.2013.06.010
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发表时间：
2013-09-17
期刊：
影响因子：
3.3
通讯作者：
Suzuki, N.
中科院分区：
文献类型：
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作者：
Sato, H.;Shibata, M.;Suzuki, N.
由于其高氧需求，神经组织易发生氧化应激。在这里，我们的目的是澄清三叉神经节中抗氧化酶的细胞定位。我们发现转录因子Sox10仅定位于成人三叉神经节的卫星胶质细胞（SGCs）。使用在Sox10启动子下表达荧光蛋白Venus的转基因小鼠，使我们能够区分神经元和SGCs。虽然超氧化物歧化酶1和超氧化物歧化酶2都存在于神经元中，但在SGCs中只发现了超氧化物歧化酶1。与过氧化氢降解相关的酶表现出不同的细胞定位，例如神经元被赋予谷胱甘肽过氧化物酶1和硫氧还蛋白2，过氧化氢酶和硫氧还蛋白2在SGCs中存在。我们的免疫组织化学结果显示，只有SGCs被氧化损伤标记物8-羟基-2'-脱氧鸟苷标记，这表明SGCs的抗氧化系统较弱。瞬时受体潜在香兰素亚家族成员1 (TRPV1)，辣椒素受体，与炎症性痛觉过敏有关，我们证明了局部使用辣椒素会导致面部短暂的机械性痛觉过敏。我们基于细胞的实验显示，TRPV1过表达的TRPV1激动剂刺激引起活性氧介导的caspase-3激活。此外，辣椒素以剂量依赖的方式诱导trpv1阳性的三叉神经节原代神经元细胞死亡，这种作用被自由基清除剂和pancaspase抑制剂抑制。本研究描述了三叉神经节中抗氧化应激相关酶的定位，揭示了活性氧在trpv1介导的caspase依赖性三叉神经节神经元细胞死亡中的关键作用。炎症性疼痛疾病应采取抗氧化应激治疗措施，防止三叉神经初级感觉神经元损伤。(c) 2013 ibro。Elsevier Ltd.出版。版权所有。
Because of its high oxygen demands, neural tissue is predisposed to oxidative stress. Here, our aim was to clarify the cellular localization of antioxidant enzymes in the trigeminal ganglion. We found that the transcriptional factor Sox10 is localized exclusively in satellite glial cells (SGCs) in the adult trigeminal ganglion. The use of transgenic mice that express the fluorescent protein Venus under the Sox10 promoter enabled us to distinguish between neurons and SGCs. Although both superoxide dismutases 1 and 2 were present in the neurons, only superoxide dismutase 1 was identified in SGCs. The enzymes relevant to hydrogen peroxide degradation displayed differential cellular localization, such that neurons were endowed with glutathione peroxidase 1 and thioredoxin 2, and catalase and thioredoxin 2 were present in SGCs. Our immunohistochemical finding showed that only SGCs were labeled by the oxidative damage marker 8-hydroxy-2'-deoxyguanosine, which indicates that the antioxidant systems of SGCs were less potent. The transient receptor potential vanilloid subfamily member 1 (TRPV1), the capsaicin receptor, is implicated in inflammatory hyperalgesia, and we demonstrated that topical capsaicin application causes short-lasting mechanical hyperalgesia in the face. Our cell-based assay revealed that TRPV1 agonist stimulation in the presence of TRPV1 overexpression caused reactive oxygen species-mediated caspase-3 activation. Moreover, capsaicin induced the cellular demise of primary TRPV1-positive trigeminal ganglion neurons in a dose-dependent manner, and this effect was inhibited by a free radical scavenger and a pancaspase inhibitor. This study delineates the localization of antioxidative stress-related enzymes in the trigeminal ganglion and reveals the importance of the pivotal role of reactive oxygen species in the TRPV1-mediated caspase-dependent cell death of trigeminal ganglion neurons. Therapeutic measures for antioxidative stress should be taken to prevent damage to trigeminal primary sensory neurons in inflammatory pain disorders. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.