Adaptive endoplasmic reticulum stress alters cellular responses to the extracellular milieu

The ability to respond to perturbations in endoplasmic reticulum (ER) function is a critical property for all cells. In the presence of chronic ER stress, the cell must adapt so that cell survival is favored or the stress may promote apoptosis. In some pathological processes, such as neurodengeneration, persistent ER stress can be tolerated for an extended period, but eventually cell death occurs. It is not known how an adaptive response converts from survival into apoptosis. To gain a better understanding of the role of adaptive ER stress in neurodegeneration, in this study, with a neuronal cell line SH‐SY5Y and primary motor neuron‐glia cell mixed cultures, we induced adaptive ER stress and modified the extracellular environment with physiologically relevant changes that alone did not activate ER stress. Our data demonstrate that an adaptive ER stress favored neuronal cell survival, but when cells were exposed to additional physiological insults the level of ER stress was increased, followed by activation of the caspase pathway. Our results indicate that an adaptive ER stress response could be converted to apoptosis when the external cellular milieu changed, suggesting that the conversion from prosurvival to proapoptotic pathways can be driven by the external milieu. This conversion was due at least partially to an increased level of ER stress. © 2015 Wiley Periodicals, Inc.     

缺血性脑卒中患者恢复稳定期外周血单个核细胞中差异表达基因的生物信息学研究

目的分析缺血性脑卒中(IS)患者恢复稳定期外周血单个核细胞(PBMCs)中的差异表达基因,为探讨脑卒中恢复稳定期的遗传病理机制提供生物信息学线索。方法选择GEO数据库中GDS4521芯片数据,该芯片以年龄、性别相匹配的20例IS恢复稳定期(脑卒中发生至少6个月以上)患者和20例未发生过脑卒中者作为研究对象,收集其PBMCs进行基因芯片检测,利用GEO2R、DAVID、g:profiler和String等工具,筛选和分析差异表达基因功能富集和相关信号通路情况。结果脑卒中恢复稳定期组与对照组相比,在PBMCs中发现37个基因表达明显变化,其中34个上升,3个下降。GO分析表明,这些差异表达基因在生物过程方面,以炎性反应、中性粒细胞趋化相关基因为最多;在分子功能方面,以趋化因子活性相关基因为最多。KEGG信号通路分析表明,位于TNF信号通路中的差异表达基因数量最多。相互作用网络图揭示,这些差异基因主要以与炎性反应相关的两个网络为主。结论 IS发生超过6个月后仍有多种功能蛋白和信号通路可能发生改变,特别是与炎性反应相关的蛋白和信号通路,提示炎性反应在IS的恢复稳定期仍可能对疾病的预后和再发起作用。     

Does ceramide play a role in neural cell apoptosis?

Ceramide is a lipid second messenger, that is generated in response to stimulation of the cell death pathways by a number of ligands binding to surface receptors, growth factor withdrawal, treatment with chemotherapeutic agents, or high doses of ionizing radiation or oxidizing agents. Depending on the target cell, ceramide induces diverse biological responses including apoptosis, cell-cycle arrest, differentiation, and also proliferation. In this review we consider the evidence for its role in apoptosis in cells of the nervous system.