Autophagy inhibits C2-ceramide-mediated cell death by decreasing the reactive oxygen species levels in SH-SY5Y cells
Autophagy inhibits C2-ceramide-mediated cell death by decreasing the reactive oxygen species levels in SH-SY5Y cells
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自噬通过降低 SH-SY5Y 细胞中活性氧水平来抑制 C2-神经酰胺介导的细胞死亡
DOI：
10.1016/j.neulet.2017.03.006
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发表时间：
2017-06
影响因子：
2.5
通讯作者：
Huang Yining
中科院分区：
文献类型：
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作者：
Fan Chenghe;Liu Yuanyuan;Zhao Mingming;Zhan Rui;Cui Wei;Jin Haiqiang;Teng Yuming;Lv Pu;Zheng Lemin;Huang Yining
神经酰胺被认为是调节神经细胞内多种过程的第二信使。然而，其在神经元自噬中的作用尚未完全了解。在这项研究中，我们使用了人类神经母细胞瘤细胞系（SH-SY 5 Y），研究C2-神经酰胺介导的细胞死亡和自噬的机制。C2-神经酰胺诱导caspase-3非依赖性细胞死亡。此外，C2-神经酰胺诱导自噬，降低Akt和mTOR的活化，增加JNK和ERK 1/2的活化。然而，只有用PD 98059抑制ERK 1/2才能阻止C2-神经酰胺诱导的自噬，表明ERK 1/2途径有助于神经酰胺诱导的自噬。根据流式细胞术测定的结果，C2-神经酰胺诱导的细胞死亡增加3-甲基腺嘌呤（3-MA）和雷帕霉素减少。此外，细胞中活性氧（ROS）的产生增加3-MA和雷帕霉素减少。基于这些数据，自噬通过减少ROS产生来保护SH-SY 5 Y细胞免于C2-神经酰胺诱导的细胞死亡。调节自噬的治疗策略可用于治疗与神经酰胺诱导的细胞死亡相关的神经系统疾病。
Ceramide has been recognized as a second messenger that regulates several intracellular processes in neuronal cells. However, its role in neuronal autophagy is not fully understood. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to investigate the mechanisms underlying C2-ceramide-mediated cell death and autophagy. C2-ceramide induced caspase-3-independent cell death. In addition, C2-ceramide induced autophagy, decreased the activation of Akt and mTOR, and increased the activation of JNK and ERK1/2. However, only inhibition of ERK1/2 with PD98059 prevented C2-ceramide-induced autophagy, indicating that the ERK1/2 pathway contributes to ceramide-induced autophagy. According to the results of the flow cytometric assays, C2-ceramide-induced cell death was increased by 3-methyadenine (3-MA) and decreased by rapamycin. Furthermore, the generation of reactive oxygen species (ROS) in the cells was increased by 3-MA and decreased by rapamycin. Based on these datas, autophagy protected SH-SY5Y cells from C2-ceramide-induced cell death by decreasing ROS production. Therapeutic strategies that regulate autophagy may be used in the treatment of neurological disorders associated with ceramide-induced cell death.
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影响因子：
8
作者：
Mencarelli, Chiara;Martinez-Martinez, Pilar
通讯作者：
Martinez-Martinez, Pilar
影响因子：
--
作者：
Jazvinšćak Jembrek M;Hof PR;Šimić G
通讯作者：
Šimić G
影响因子：
13.3
作者：
Deroyer, Celine;Renert, Anne-Francoise;Fillet, Marianne
通讯作者：
Fillet, Marianne
影响因子：
2.5
作者：
Mohan N;Banik NL;Ray SK
通讯作者：
Ray SK
DOI：
10.1038/nrm3735
发表时间：
2014-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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