Ischemia preconditioning protects astrocytes from ischemic injury through 14‐3‐3γ
Ischemia preconditioning protects astrocytes from ischemic injury through 14‐3‐3γ
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DOI：
10.1002/jnr.23574
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发表时间：
2015-10
影响因子：
4.2
通讯作者：
Y. Pang;Chao Rui Chai;K. Gao;X. Jia;J. Kong;X. Chen;G. Vatcher;Jian Guo Chen;A. Yu
中科院分区：
文献类型：
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作者：
Y. Pang;Chao Rui Chai;K. Gao;X. Jia;J. Kong;X. Chen;G. Vatcher;Jian Guo Chen;A. Yu
中风是导致死亡和残疾的主要原因，需要新的策略来减少神经元损伤和改善预后。缺血预适应(IPC)是一种保护细胞免受后续缺血损伤的内在现象，可能为临床治疗提供新的机制。在这项研究中，原代星形胶质细胞暴露在不同的IPC持续时间(15、30、60或120分钟)时，细胞死亡显著低于对照组。15分钟是保护星形胶质细胞免受8小时缺血损伤的最有效的IPC。IPC的保护机制包括上调14-3-3ATP等保护性蛋白，减少丙二醛含量和γ耗竭。14-3-3γ是一种抗细胞凋亡的细胞内蛋白，在IPC后84小时内显著上调。此外，IPC还可促进c-jun氨基末端激酶、细胞外信号相关激酶−1/2、p38和蛋白激酶B信号通路的激活。当SP600125特异性地抑制JNK时，IPC诱导的14-3-3γ上调几乎完全消失，但对其水平无明显影响。这表明，即使能量保存和14-3-3γ上调都被IPC启动，但它们是由不同的途径控制的。ERK1/2、p38和Akt信号通路不参与14-3-3γ的上调和能量保存。这些结果表明，缺血预适应可通过诱导14-3-3γ和通过不同途径减轻能量消耗来保护星形胶质细胞免受缺血损伤，提示缺血预适应具有多重保护作用，为潜在的卒中治疗提供了新的思路。©2015 Wiley期刊，Inc.
Stroke is a leading cause of death and disability, and new strategies are required to reduce neuronal injury and improve prognosis. Ischemia preconditioning (IPC) is an intrinsic phenomenon that protects cells from subsequent ischemic injury and might provide promising mechanisms for clinical treatment. In this study, primary astrocytes exhibited significantly less cell death than control when exposed to different durations of IPC (15, 30, 60, or 120 min). A 15‐min duration was the most effective IPC to protect astrocytes from 8‐hr‐ischemia injury. The protective mechanisms of IPC involve the upregulation of protective proteins, including 14‐3‐3γ, and attenuation of malondialdehyde (MDA) content and ATP depletion. 14‐3‐3γ is an antiapoptotic intracellular protein that was significantly upregulated for up to 84 hr after IPC. In addition, IPC promoted activation of the c‐Jun N‐terminal kinase (JNK), extracellular signal‐related kinase (ERK)−1/2, p38, and protein kinase B (Akt) signaling pathways. When JNK was specifically inhibited with SP600125, the upregulation of 14‐3‐3γ induced by IPC was almost completely abolished; however, there was no effect on ATP or MDA levels. This suggests that, even though both energy preservation and 14‐3‐3γ up‐regulation were turned on by IPC, they were controlled by different pathways. The ERK1/2, p38, and Akt signaling pathways were not involved in the 14‐3‐3γ upregulation and energy preservation. These results indicate that IPC could protect astrocytes from ischemia injury by inducing 14‐3‐3γ and by alleviating energy depletion through different pathways, suggesting multiple protection of IPC and providing new insights into potential stroke therapies. © 2015 Wiley Periodicals, Inc.