Profiling the Expression of Endoplasmic Reticulum Stress Associated Heat Shock Proteins in Animal Epilepsy Models
Profiling the Expression of Endoplasmic Reticulum Stress Associated Heat Shock Proteins in Animal Epilepsy Models
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DOI：
10.1016/j.neuroscience.2019.12.015
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发表时间：
2020-03-01
期刊：
影响因子：
3.3
通讯作者：
Potschka, Heidrun
中科院分区：
文献类型：
--
作者：
Nowakowska, Marta;Gualtieri, Fabio;Potschka, Heidrun
未折叠蛋白反应是由内质网中错误折叠的蛋白质触发的信号级联反应。热休克蛋白H4（HSPH4）和A5（HSPA5）是存在于细胞器内的两种伴侣蛋白，其在长时间应激条件下靶向错误折叠的肽。致痫性损伤和癫痫发作是细胞应激的显著来源。为了研究它们是否影响这些分子伴侣的表达，我们在经历癫痫持续状态（SE）作为癫痫发生的触发因素的大鼠和犬癫痫患者的大脑中进行了免疫组织化学染色。HSPA5和HSPH4的定量显示海马和海马旁皮质的改变。在大鼠中，SE诱导梨状皮质中HSPA5的上调和海马中HSPA5和HSPH4的下调。在自发性复发性癫痫发作的慢性期观察到这两种蛋白质表达的区域性限制性增加。共聚焦显微镜显示两种蛋白在神经元中的主要表达，在小胶质细胞中无表达，在星形胶质细胞中有限制性表达。在犬患者中，在诊断为结构性癫痫的动物中，仅在角Ammonis 1区域观察到HSPH4表达上调。HSPA5和HSPH4表达的这种表征提供了关于SE诱导的癫痫发生和癫痫表现后这两种蛋白质的空间和时间改变的广泛信息。这两种蛋白质的上调意味着在这些疾病阶段对ER施加压力。两者结合表明癫痫发生对HSPA5和HSPH4表达的不同影响，并表明它们是未折叠蛋白反应药理学调节的可能靶点。(C)2020年，任作家。由Elsevier Ltd代表IBRO出版。
Unfolded protein response is a signaling cascade triggered by misfolded proteins in the endoplasmic reticulum. Heat shock protein H4 (HSPH4) and A5 (HSPA5) are two chaperoning proteins present within the organelle, which target misfolded peptides during prolonged stress conditions. Epileptogenic insults and epileptic seizures are a notable source of stress on cells. To investigate whether they influence expression of these chaperones, we performed immunohistochemical stainings in brains from rats that experienced a status epilepticus (SE) as a trigger of epileptogenesis and from canine epilepsy patients. Quantification of HSPA5 and HSPH4 revealed alterations in hippocampus and parahippocampal cortex. In rats, SE induced up-regulation of HSPA5 in the piriform cortex and down-regulation of HSPA5 and HSPH4 in the hippocampus. Regionally restricted increases in expression of the two proteins has been observed in the chronic phase with spontaneous recurrent seizures. Confocal microscopy revealed a predominant expression of both proteins in neurons, no expression in microglia and circumscribed expression in astroglia. In canine patients, only up-regulation of HSPH4 expression was observed in Cornu Ammonis 1 region in animals diagnosed with structural epilepsy. This characterization of HSPA5 and HSPH4 expression provided extensive information regarding spatial and temporal alterations of the two proteins during SE-induced epileptogenesis and following epilepsy manifestations. Up-regulation of both proteins implies stress exerted on ER during these disease phases. Taken together suggest a differential impact of epileptogenesis on HSPA5 and HSPH4 expression and indicate them as a possible target for pharmacological modulation of unfolded protein response. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of IBRO.