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.

中文翻译：

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分析内质网应激相关热休克蛋白在动物癫痫模型中的表达。

未折叠的蛋白质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) 是细胞器中存在的两种伴侣蛋白，它们在长时间的压力条件下靶向错误折叠的肽。致癫痫性损伤和癫痫发作是细胞压力的显着来源。为了研究它们是否影响这些伴侣的表达，我们对经历癫痫持续状态 (SE) 作为癫痫发生触发因素的大鼠和犬癫痫患者的大脑进行了免疫组织化学染色。HSPA5 和 HSPH4 的量化揭示了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限制性增加。共聚焦显微镜显示两种蛋白质在神经元中的主要表达，在小胶质细胞中没有表达，在星形胶质细胞中表达有限。在犬科患者中，在诊断为结构性癫痫的动物中，仅在 Cornu 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 诱导的癫痫发生过程和癫痫表现后两种蛋白质的空间和时间变化的广泛信息。两种蛋白质的上调意味着在这些疾病阶段对 ER 施加压力。