Han Lijian, Ni Yaohui, Cao Maohong, Zhu Liang, Dai Aihua, Xu Zhiwei, Liu Xiaorong, Chen Rongrong, Ning Xiaojin, Ke Kaifu
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Cell Mol Neurobiol. 2016 Jul;36(5):713-24. doi: 10.1007/s10571-015-0251-1. Epub 2015 Aug 5.
Interferon gamma-induced GTPase (IGTP), which is also named Irgm3, has been widely described in regulating host resistance against intracellular pathogens. Previous researches have demonstrated that IGTP exerts beneficial function during coxsackievirus B3 (CVB3) infection. However, little information is available regarding the role of IGTP in central nervous system. Here, our study revealed that IGTP may have an essential role during ICH-induced neuronal apoptosis. We found the expression level of IGTP adjacent to hematoma was strongly increased after ICH, accompanied with the up-regulation of proliferating cell nuclear antigen (PCNA), active-caspase-3, p-GSK-3β, and Bax. IGTP was also observed to be co-localized with PCNA in astrocytes and active-caspase-3 in neurons, indicating its association with astrocyte proliferation and neuronal apoptosis after ICH. Finally, in vitro study, knocking down IGTP with IGTP-specific siRNA promoted active-caspase-3, p-GSK-3β, and Bax expression, and led to more severe neuronal apoptosis after ICH. All these results above suggested that IGTP might play a critical role in protecting neurons from apoptosis after ICH.
干扰素γ诱导的GTP酶(IGTP),也被称为Irgm3,在调节宿主对细胞内病原体的抵抗力方面已有广泛描述。先前的研究表明,IGTP在柯萨奇病毒B3(CVB3)感染期间发挥有益作用。然而,关于IGTP在中枢神经系统中的作用,目前所知甚少。在此,我们的研究表明,IGTP可能在脑出血(ICH)诱导的神经元凋亡过程中发挥重要作用。我们发现,ICH后血肿周围IGTP的表达水平显著升高,同时增殖细胞核抗原(PCNA)、活化的半胱天冬酶-3、磷酸化糖原合成酶激酶-3β(p-GSK-3β)和Bax的表达也上调。还观察到IGTP与星形胶质细胞中的PCNA以及神经元中的活化半胱天冬酶-3共定位,表明其与ICH后星形胶质细胞增殖和神经元凋亡有关。最后,在体外研究中,用IGTP特异性小干扰RNA敲低IGTP可促进活化半胱天冬酶-3、p-GSK-3β和Bax的表达,并导致ICH后更严重的神经元凋亡。上述所有结果表明,IGTP可能在保护ICH后神经元免于凋亡方面发挥关键作用。