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Neuronic autophagy contributes to p-connexin 43 degradation in hippocampal astrocytes following traumatic brain injury in rats

机译:大鼠脑外伤后神经元自噬导致海马星形胶质细胞中p-connexin 43降解

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摘要

Connexins, gap junction proteins, have short half-lives of only a few hours; therefore, degradation of these proteins can rapidly modulate their function. Autophagy is a type of degradation pathway that has been implicated in several diseases and was reported to be induced following traumatic brain injury (TBI). The aim of the present study was to investigate the involvement of neuronic autophagy in proteolysis of phosphorylated connexin 43 (p-Cx43) in hippocampal astrocytes following TBI in rats. Western blot analysis and immunofluorescence showed a TBI-induced increase in levels of astrocytic p-Cx43 following treatment with 3-methyladenine, an inhibitor of autophagy, in the hippocampus. Internalized gap junctions were observed in the neuronic cytoplasm using transmission electron microscopy. These results demonstrated that neuronic autophagy may regulate cellular levels of p-Cx43 in hippocampal astrocytes following TBI. This therefore indicated that the persistence of p-Cx43 accumulation was due to insufficient degradation capacity of constitutive autophagy.
机译:连接蛋白,间隙连接蛋白,半衰期短,只有几个小时。因此,这些蛋白质的降解可以迅速调节其功能。自噬是一种降解途径,已与多种疾病相关,据报道是在颅脑外伤(TBI)后诱发的。本研究的目的是研究神经元自噬与大鼠TBI后海马星形胶质细胞磷酸化连接蛋白43(p-Cx43)的蛋白水解有关。 Western印迹分析和免疫荧光显示,海马中TBI诱导的自噬抑制剂3-甲基腺嘌呤处理后星形细胞p-Cx43水平增加。使用透射电子显微镜在神经细胞质中观察到内在的间隙连接。这些结果表明,神经元自噬可能调节TBI后海马星形胶质细胞中p-Cx43的细胞水平。因此,这表明p-Cx43积累的持久性是由于组成型自噬的降解能力不足所致。

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