S100B potently activates p65/c-Rel transcriptional complexes in hippocampal neurons:: clinical implications for the role of S100B in excitotoxic brain injury
S100B potently activates p65/c-Rel transcriptional complexes in hippocampal neurons:: clinical implications for the role of S100B in excitotoxic brain injury
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DOI：
10.1016/j.neuroscience.2004.06.013
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Prehn, JHM
中科院分区：
文献类型：
--
作者：
Kögel, D;Peters, M;Prehn, JHM
血清S100B水平升高与多种形式的中枢神经系统损害呈正相关，如中风、中枢神经系统创伤和神经退行性疾病，但在精神障碍中也是如此。然而，目前尚不清楚血清S100B水平升高是否反映了神经再生或神经退行性反应，由于谷氨酸受体过度激活(兴奋性毒性)可能参与精神障碍的神经元病理，我们研究了S100B在N-甲基-D-天冬氨酸(NMDA)诱导的神经细胞死亡中的作用。在这里，我们证明了非常低浓度的S100B通过激活REL/核因子kappaB(NF-kappaB)家族的转录因子来显著保护原代大鼠海马神经元免受NMDA毒性。进一步的实验表明：1)S100B激活了神经元中晚期糖基化产物受体(RAGE)基因的表达；2)S100B诱导了由p65和c-Rel亚基组成的活性核因子-kappaB复合体的独特组成，提示了一种参与S100B介导的神经保护的新机制。我们的数据表明，在脑损伤的神经胶质反应中分泌的S100B以一种RAGE依赖的方式有效地激活P65/c-Rel，并可能在精神障碍中发挥神经保护和神经再生的作用。(C)2004年IBRO。爱思唯尔有限公司出版。保留所有权利。
increased serum levels of S100B are positively correlated with multiple forms of CNS damage, such as stroke, CNS trauma and neurodegenerative diseases, but also in psychiatric disorders. However, it is currently not known whether increased serum levels of S100B reflect a neuroregenerative or neurodegenerative response, Since glutamate receptor overactivation (excitotoxicity) may contribute to neuronal pathology in psychiatric disorders, we investigated the effect of S100B on N-methyl-D-aspartate (NMDA)-induced neuronal cell death. Here we demonstrate that very low concentrations of S100B significantly protect primary rat hippocampal neurons against NMDA toxicity by activation of transcription factors of the Rel/nuclear factor kappaB (NF-kappaB) family. Further experiments suggest that i) S100B activated expression of the receptor of advanced glycation products (RAGE) gene in neurons and ii) S100B induced a unique composition of the active NF-kappaB complex consisting of the p65 and c-Rel subunits suggesting a novel mechanism for NF-kappaB activation involved in S100B-mediated neuroprotection. Our data suggest that S100B secreted during the glial response to brain injury potently activates p65/c-Rel in a RAGE-dependent manner and may exert neuroprotective and neuroregenerative effects in psychiatric disorders. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.