[Exogenous EPO protects HT22 cells from intermittent hypoxia-induced injury by activating JAK2-STAT5 signaling pathway].

Q3 Medicine 生理学报 Pub Date : 2024-10-25
Ke-Rong Qi, Xue Chen, Jian-Chao Si, Qing-Qing Liu, Sheng-Chang Yang
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引用次数: 0

Abstract

The aim of this study was to investigate the effects of exogenous erythropoietin (EPO) on intermittent hypoxia (IH)-induced neuronal injury and the underlying mechanism. Mouse hippocampal neuron HT22 cells were exposed to IH for different durations (1% O2 for 7 min/21% O2 for 3 min, one cycle for 10 min). Cell viability was detected by CCK-8. EPO content in the supernatant of cell culture medium was detected by ELISA kit, and the protein expression was detected by Western blot. EPO receptor (EPOR) protein expression was detected by immunofluorescence staining and Western blot. Cellular apoptosis and mitochondrial membrane potential were detected by the corresponding kits. Reactive oxygen species (ROS) level was detected by DCFH probe, and expression levels of JAK2-STAT5 signaling pathway-related proteins were detected by Western blot. The results showed that IH exposure significantly decreased HT22 cell activity. EPO and EPOR protein expressions were significantly up-regulated at 12 h of IH exposure, but down-regulated at 24 and 48 h. In IH-treated HT22 cells, exogenous EPO significantly increased cell activity and mitochondrial membrane potential, decreased ROS levels and cell apoptosis, up-regulated Nrf-2 and heme oxygenase 1 (HO-1) protein expression levels, decreased Cleaved-Caspase-3/Caspase-3 and Bax/Bcl-2 ratios, and promoted the phosphorylation of JAK2-STAT5 pathway-related proteins. Whereas JAK2 and STAT5 blockers both reversed these neuronal protective effects of EPO. These results suggest exogenous EPO inhibits IH-induced oxidative stress and apoptosis by activating the JAK2-STAT5 signaling pathway, thus exerting a neuronal protective effect.

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[外源性 EPO 通过激活 JAK2-STAT5 信号通路保护 HT22 细胞免受间歇性缺氧诱导的损伤】。]
本研究旨在探讨外源性促红细胞生成素(EPO)对间歇性缺氧(IH)诱导的神经元损伤的影响及其内在机制。小鼠海马神经元HT22细胞暴露于不同持续时间的间歇缺氧(1%氧气7分钟/21%氧气3分钟,一个周期10分钟)。用 CCK-8 检测细胞活力。用酶联免疫吸附试剂盒检测细胞培养液上清液中的 EPO 含量,并用 Western 印迹法检测其蛋白表达。通过免疫荧光染色和 Western 印迹检测 EPO 受体(EPOR)蛋白的表达。细胞凋亡和线粒体膜电位由相应的试剂盒检测。活性氧(ROS)水平通过 DCFH 探针检测,JAK2-STAT5 信号通路相关蛋白的表达水平通过 Western 印迹检测。结果表明,IH暴露会明显降低HT22细胞的活性。EPO和EPOR蛋白表达在IH暴露12 h时明显上调,但在24 h和48 h时下调。在IH处理的HT22细胞中,外源性EPO能明显提高细胞活性和线粒体膜电位,降低ROS水平和细胞凋亡,上调Nrf-2和血红素加氧酶1(HO-1)蛋白表达水平,降低裂解-Caspase-3/Caspase-3和Bax/Bcl-2比值,促进JAK2-STAT5通路相关蛋白的磷酸化。而JAK2和STAT5阻断剂都能逆转EPO对神经元的保护作用。这些结果表明,外源性 EPO 可通过激活 JAK2-STAT5 信号通路抑制 IH 诱导的氧化应激和细胞凋亡,从而发挥保护神经元的作用。
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来源期刊
生理学报
生理学报 Medicine-Medicine (all)
CiteScore
1.20
自引率
0.00%
发文量
4820
期刊介绍: Acta Physiologica Sinica (APS) is sponsored by the Chinese Association for Physiological Sciences and Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences (CAS), and is published bimonthly by the Science Press, China. APS publishes original research articles in the field of physiology as well as research contributions from other biomedical disciplines and proceedings of conferences and symposia of physiological sciences. Besides “Original Research Articles”, the journal also provides columns as “Brief Review”, “Rapid Communication”, “Experimental Technique”, and “Letter to the Editor”. Articles are published in either Chinese or English according to authors’ submission.
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