Autophagy triggers endoplasmic reticulum stress and C/EBP homologous protein-mediated apoptosis in OGD/R-treated neurons in a caspase-12-independent manner

切碎 未折叠蛋白反应 细胞生物学 自噬 细胞凋亡 内质网 化学 程序性细胞死亡 半胱氨酸蛋白酶12 信号转导 ATF4 半胱氨酸蛋白酶 生物 生物化学
作者
Ying Tian,Liang Wang,Zhiqiang Qiu,Yulun Xu,Rongrong Hua
出处
期刊:Journal of Neurophysiology [American Physiological Society]
卷期号:126 (5): 1740-1750 被引量:11
标识
DOI:10.1152/jn.00649.2020
摘要

We reported that a high level of autophagy was initiated by oxygen-glucose deprivation (OGD) and was maintained in neurons even after oxygen-glucose deprivation followed by reoxygenation (OGD/R), accompanied by neuronal apoptosis. This study focused on autophagy-induced apoptosis and its signaling network, especially the role of endoplasmic reticulum stress (ERS). Analysis of primary cultured cortical neurons from mice showed that the autophagy-induced apoptosis depended on caspase-8 and -9 but not on caspase-12. This finding did not mean that the endoplasmic reticulum did not participate in this process. Increases in the levels of endoplasmic reticulum (ER) biomarkers and binding immunoglobulin protein (BiP) were induced by autophagy in OGD/R-treated neurons. In addition, as an apoptotic transcription factor induced by ER stress, C/EBP homologous protein (CHOP) expression was significantly increased in neurons after OGD/R. This result suggested that the autophagy-BiP-CHOP-caspase (8 and 9)-dependent apoptotic signaling pathway at least partly participated in autophagy-induced apoptosis in primary cortical neurons. It revealed that ER induced apoptosis in neurons suffering from OGD/R injury in an ER stress-CHOP-dependent manner rather than a caspase-12-dependent manner. However, more research on signaling or cross-linking networks and intermediate links is needed. The realization of caspase-12-independent BiP-CHOP neuronal apoptosis pathway has expanded our understanding of the neuronal apoptosis network, which may eventually provide endogenous interventional strategies for OGD/R injury after stroke.NEW & NOTEWORTHY ER stress induced by autophagy mediates caspase-8- and caspase-9-dependent apoptosis pathways by regulating CHOP in neurons exposed to OGD/R. We hypothesized that the autophagy-BiP-CHOP-caspase (8 and 9)-dependent apoptotic signaling pathway at least partly participated in autophagy-induced apoptosis in primary cortical neurons.
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