Zhao Zhao-Hua, Deng Bin, Xu Hao, Zhang Jun-Feng, Mi Ya-Jing, Meng Xiang-Zhong, Gou Xing-Chun, Xu Li-Xian
Department of Anesthesiology, College of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
Institute of Basic and Translational Medicine & School of Basic Medical Sciences, Xi'an Medical University, Xi'an, 710021, China.
Cell Mol Neurobiol. 2017 May;37(4):707-715. doi: 10.1007/s10571-016-0406-8. Epub 2016 Jul 21.
Previous studies have proven that paired immunoglobulin-like receptor B (PirB) plays a crucial suppressant role in neurite outgrowth and neuronal plasticity after central nervous system injury. However, the role of PirB in neuronal survival after cerebral ischemic injury and its mechanisms remains unclear. In the present study, the role of PirB is investigated in the survival and apoptosis of cerebral cortical neurons in cultured primary after oxygen and glucose deprivation (OGD)-induced injury. The results have shown that rebarbative PirB exacerbates early neuron apoptosis and survival. PirB gene silencing remarkably decreases early apoptosis and promotes neuronal survival after OGD. The expression of bcl-2 markedly increased and the expression of bax significantly decreased in PirB RNAi-treated neurons, as compared with the control- and control RNAi-treated ones. Further, phosphorylated TrkB and mTOR levels are significantly downregulated in the damaged neurons. However, the PirB silencing markedly upregulates phosphorylated TrkB and mTOR levels in the neurons after the OGD. Taken together, the overexpression of PirB inhibits the neuronal survival through increased neuron apoptosis. Importantly, the inhibition of the phosphorylation of TrkB and mTOR may be one of its mechanisms.
先前的研究已经证明，配对免疫球蛋白样受体B（PirB）在中枢神经系统损伤后的神经突生长和神经元可塑性中起着至关重要的抑制作用。然而，PirB在脑缺血损伤后神经元存活中的作用及其机制仍不清楚。在本研究中，研究了PirB在氧糖剥夺（OGD）诱导损伤后原代培养的大脑皮质神经元存活和凋亡中的作用。结果表明，令人讨厌的PirB会加剧早期神经元凋亡并影响存活。PirB基因沉默显著减少早期凋亡并促进OGD后神经元的存活。与对照和对照RNAi处理的神经元相比，PirB RNAi处理的神经元中bcl-2的表达明显增加，bax的表达明显降低。此外，受损神经元中磷酸化的TrkB和mTOR水平显著下调。然而，PirB沉默显著上调了OGD后神经元中磷酸化的TrkB和mTOR水平。综上所述，PirB的过表达通过增加神经元凋亡来抑制神经元存活。重要的是，抑制TrkB和mTOR的磷酸化可能是其机制之一。
