Activated mGluR5 protects BV2 cells against OGD/R induced cytotoxicity by modulating BDNF-TrkB pathway
Activated mGluR5 protects BV2 cells against OGD/R induced cytotoxicity by modulating BDNF-TrkB pathway
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激活的 mGluR5 通过调节 BDNF-TrkB 途径保护 BV2 细胞免受 OGD/R 诱导的细胞毒性。
DOI：
10.1016/j.neulet.2017.06.029
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发表时间：
2017
影响因子：
2.5
通讯作者：
Cui Guiyun
中科院分区：
文献类型：
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作者：
Ye Xinchun;Yu Lu;Zuo D;an;Zhang Liang;Zu Jie;Hu Jinxia;Tang Jiao;Bao Lei;Cui Chengcheng;Zhang Ruixue;Jin Guoliang;Zan Kun;Zhang Zuohui;Yang Xinxin;Shi Hongjuan;Zhang Zunsheng;Xiao Qihua;Liu Yonghai;Xiang Jie;Zhang Xueling;Cui Guiyun
代谢型谷氨酸受体5（mGluR 5）对缺血性脑损伤具有保护作用，但其机制尚不清楚。脑源性神经营养因子（Brain-derived neurotrophic factor，BDNF）是神经营养因子家族中的重要成员，其保护作用是通过与高亲和力受体酪氨酸蛋白激酶B（Trk B）结合而实现的。为了研究活化的mGluR 5对抗氧-葡萄糖剥夺（OGD）/再氧合（R）介导的细胞毒性的作用，在有或没有OGD/R暴露的BV 2细胞（小胶质细胞系）中评价细胞活力、凋亡、炎性细胞因子的释放和活性氧簇（ROS）的积累。我们的数据表明，CHPG（选择性mGluR 5激动剂）预处理，作为mGluR 5激动剂，保护BV 2细胞免受OGD/R诱导的细胞毒性，凋亡，炎性细胞因子的释放，和ROS的积累。然而，这些作用被mGluR 5拮抗剂MPEP预处理显著逆转。我们的数据还显示，BDNF和TrkB在BV 2细胞中的表达与OGD/R暴露显著降低。CHPG预处理可显著增强OGD/R诱导的BV 2细胞BDNF和TrkB的表达。然而，MPEP预处理可显著消除增加的表达。此外，K252 a抑制BDNF/TrKB通路也减弱了活化的mGluR 5对OGD/R诱导的细胞毒性、凋亡和炎性细胞因子释放的保护作用。此外，外源性BDNF预处理可保护BV 2细胞免受OGD/R诱导的细胞凋亡和炎性细胞因子的释放。提示BDNF/TrKB通路可能参与调节激活的mGluR 5对OGD/R诱导的BV 2细胞毒性的保护作用。
Activated Metabotropic glutamate receptors 5(mGluR5) exhibits protective effects against ischemic brain damage, but the underlying mechanisms are not clearly known. Brain-derived neurotrophic factor (BDNF), as a valuable member of neurotrophic factor family, exerts its protection by combining with its high-affinity receptor tyrosine protein kinase B (TrkB). To investigate the role of activated mGluR5 against oxygen-glucose deprivation (OGD)/reoxygenation (R)-mediated cytotoxicity, the cell viability, apoptosis, the release of inflammatory cytokines and accumulation of reactive oxygen species (ROS) were evaluated in BV2 cells (Microglia cell line) with or without OGD/R exposure. Our data show that CHPG (the selective mGluR5 agonist) pretreatment, as an mGluR5 agonist, protected BV2 cells against OGD/R-induced cytotoxicity, apoptosis, the release of inflammatory cytokines, and the accumulation of ROS. However, these effects were significantly reversed by the mGluR5 antagonist MPEP pretreatment. Our data also show that the expressions of BDNF and TrkB were significantly decreased in BV2 cells with OGD/R exposure. CHPG pretreatment significantly enhanced the expressions of BDNF and TrkB in BV2 cells with OGD/R exposure. However, the increased expressions were significantly abrogated by MPEP pretreatment. In addition, inhibition of BDNF/TrKB pathway by K252a also attenuated the protective effects of activated mGluR5 against OGD/R-induced cytotoxicity, apoptosis and the release of inflammatory cytokines. Morever, pretreatment with exogenous BDNF protected BV2 cells against OGD/R induced apoptosis and release of inflammatory cytokines. These data suggested that BDNF/TrKB pathway may be involved in regulating activated mGluR5′ protective effects against OGD/R induced cytotoxicity in BV2 cells.