Upregulation of PLZF is Associated with Neuronal Injury in Lipopolysaccharide-Induced Neuroinflammation
Upregulation of PLZF is Associated with Neuronal Injury in Lipopolysaccharide-Induced Neuroinflammation
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DOI：
10.1007/s11064-016-2027-5
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发表时间：
2016-11-01
影响因子：
4.4
通讯作者：
Lu, Xiang
中科院分区：
文献类型：
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作者：
He, Mingqing;Liu, Yonghua;Lu, Xiang
早幼粒细胞白血病锌指（PLZF）蛋白已被鉴定为多种癌症的肿瘤抑制因子，包括白血病、恶性间皮瘤、恶性黑色素瘤、胰腺癌和前列腺癌。研究表明，PLZF的表达改变影响其与肿瘤发生相关的生物学功能，如增殖、细胞周期和凋亡。然而，关于其在中枢神经系统疾病中的调节和可能功能的信息仍然有限。在这项研究中，我们进行了一个神经炎症模型，通过脂多糖（LPS）注射在成年大鼠侧脑室和检测PLZF表达增加的大脑皮层。免疫荧光检测显示，注射LPS后第3天，PLZF在神经元中显著增加，而在星形胶质细胞和小胶质细胞中没有增加。此外，在体内和体外研究中，活性caspase-3、细胞周期蛋白D1和CDK 4也同时上调。此外，这些蛋白质在皮质原代神经元中的表达被siRNA敲低PLZF后抑制。总的来说，所有这些结果都表明PLZF的上调可能参与了LPS注射后神经炎症中神经元的凋亡样损伤。
Promyelocytic leukemia zinc finger (PLZF) protein has been identified as a tumor suppressor in a variety of cancers, including leukemia, malignant mesothelioma, malignant melanoma, pancreatic cancer and prostate cancer. Studies have demonstrated that altered expression of PLZF affected its biological functions associated with tumorigenesis, such as proliferation, cell cycle, and apoptosis. However, information regarding its regulation and possible function in the central nervous system diseases is still limited. In this study, we performed a neuroinflammatory model by lipopolysaccharide (LPS) lateral ventricle injection in adult rats and detected increased expression of PLZF in the brain cortex. Immunofluorescence assay indicated that PLZF was significantly increased in neurons 3 day after LPS injection, but not in astrocytes and microglia. Moreover, there was a concomitant upregulation of active caspase-3, cyclin D1, and CDK4 in vivo and vitro studies. In addition, the expression of these proteins in cortical primary neurons was inhibited after knocking down PLZF by siRNA. Collectively, all these results suggested that the upregulation of PLZF might be involved in neuronal apoptotic-like injury in neuroinflammation after LPS injection.