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首页> 外文期刊>Cellular Signalling >Orexin-A protects against oxygen-glucose deprivation/reoxygenation-induced cell damage by inhibiting endoplasmic reticulum stress-mediated apoptosis via the Gi and PI3K signaling pathways
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Orexin-A protects against oxygen-glucose deprivation/reoxygenation-induced cell damage by inhibiting endoplasmic reticulum stress-mediated apoptosis via the Gi and PI3K signaling pathways

机译：orexin-a通过抑制通过gi和pi3k信号通路抑制内质网胁迫介导的凋亡来保护氧葡萄糖剥夺/雷诺毒性诱导的细胞损伤

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摘要

The neuropeptide orexin-A (OXA) has a neuroprotective effect, acting as an anti-apoptotic factor in response to multiple stimuli. Apoptosis induced by endoplasmic reticulum stress (ERS) underlies oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell damage, an in vitro model of ischemia/reperfusion injury. However, that OXA inhibits ERS-induced apoptosis in the OGD/R model has not been reported. In the present study, we investigated the neuroprotective effect of OXA (0.1 mu M) on OGD/R-induced damage in the human neuroblastoma cell line SH-SY5Y. After OXA treatment following 4 h oxygen-glucose deprivation (OGD) and then 4 h reoxygenation (R), cell morphology, viability, and apoptosis were analyzed by histology, Cell Counting Kit-8 assay, and flow cytometry, respectively. Western blotting was used to measure expression levels of ERS- and apoptosis-related proteins. To determine signaling pathways involved in OXA-mediated neuroprotection, the Gi pathway inhibitor pertussis toxin (PTX; 100 ng/mL) and PI3K inhibitor LY294002 (LY; 10 mu M) were added. In addition, in order to prove the specificity of these characteristics, the OXA antagonist Suvorexant (DORA; Ki of 0.55 nM and 0.35 nM for OX1R and OX2R) was used for intervention. Our results showed that OGD/R induced cell damage, manifested as morphological changes and a significant decrease in viability. Furthermore, Western blotting detected an increase in ERS-related proteins GRP78, p-IRE1 alpha, p-JNK, and Cleaved caspase-12, as well as apoptosis-related proteins Cleaved caspase-3 and Bax, and a decrease in the anti-apoptosis factor Bcl-2. OXA intervention alleviated the degree of cellular damage, and protein expression was also reversed. In addition, the protective effect of OXA was reduced by adding PTX and LY. Meanwhile, after the use of DORA, changes in the expression of related proteins were detected, and it was found that the protective effect of OXA was weakened. Collectively, our results indicate
机译：神经肽orexin-a（OXA）具有神经保护作用，作用为响应多种刺激的抗凋亡因子。内质网应激诱导的细胞凋亡抗氧 - 葡萄糖剥夺和重新氧化（OGD / R）诱导的细胞损伤，其缺血/再灌注损伤的体外模型。然而，尚未报道尚未报道OGD / R模型中的OXA抑制诱导的细胞凋亡。在本研究中，我们研究了OXA（0.1μm）对人神经母细胞瘤细胞系SH-SY5Y中OGD / R诱导的损伤的神经保护作用。通过组织学，细胞计数试剂盒-8测定和流式细胞术分析4小时氧葡萄糖剥夺（OGD），然后分析细胞形态，活力和细胞凋亡后，分析细胞形态，活力和细胞凋亡。用于测量与凋亡相关蛋白质和凋亡相关蛋白的表达水平的蛋白质印迹。为了确定涉及氧气介导的神经保护的信号传导途径，加入GI途径抑制剂豆类毒素（PTX; 100ng / ml）和PI3K抑制剂Ly294002（Ly;10μm）。另外，为了证明这些特征的特异性，氧气拮抗剂Suvorexant（Dora; ki为0.55nm和0.35nm，ox1r和Ox2r的ki）用于干预。我们的结果表明，OGD / R诱导细胞损伤，表现为形态学变化和可行性的显着降低。此外，Western Blotting检测到ERS相关蛋白GRP78，P-IRE1α，P-JNK和切割的Caspase-12的增加，以及凋亡相关的蛋白质切割的Caspase-3和Bax，以及抗的降低凋亡因子Bcl-2。牛粪干预减轻了细胞损伤程度，蛋白质表达也逆转。此外，通过添加PTX和LY来降低OXA的保护作用。同时，在使用DORA之后，检测到相关蛋白表达的变化，发现氧气的保护作用被削弱。集体，我们的结果表明

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