NEUROPROTECTIVE MECHANISM OF LOW-DOSE SODIUM NITRITE IN OXYGEN-GLUCOSE DEPRIVATION MODEL OF CEREBRAL ISCHEMIC STROKE IN PC12 CELLS
NEUROPROTECTIVE MECHANISM OF LOW-DOSE SODIUM NITRITE IN OXYGEN-GLUCOSE DEPRIVATION MODEL OF CEREBRAL ISCHEMIC STROKE IN PC12 CELLS
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DOI：
10.17179/excli2018-1947
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发表时间：
2019-01-01
期刊：
影响因子：
4.6
通讯作者：
Rasmi, Yousef
中科院分区：
文献类型：
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作者：
Shakib, Nader;Ansari, Mohammad Hassan Khadem;Rasmi, Yousef
本研究旨在探讨低剂量亚硝酸钠（SN）对缺糖缺氧（OGD）诱导的PC 12细胞内质网（ER）应激的保护作用及其机制。将PC 12细胞暴露于4小时的OGD并用100 μ mol SN处理。免疫印迹法检测ER应激标志物PKR样内质网激酶（PERK）、转录因子6（ATF 6）、CCAAT/增强子结合蛋白同源蛋白（CHOP）以及caspase-12和caspase-3的表达和活性。荧光染色检测ER活性氧（ROS）和Ca 2+释放水平。MTT法检测细胞活力。结果表明，SN能显著抑制OGD损伤的PC 12细胞内质网ROS的产生和Ca ~（2+）的释放。SN处理后，OGD损伤的PC 12细胞中ER应激标志物表达和caspase-3和-12裂解片段减少。这些发现伴随着细胞活力的显著增加。看来SN至少部分地通过减少由OGD损伤引起的ROS介导的ER应激来发挥神经保护作用。
The purpose of this study was to clarify the mechanisms of the protective effects of low-dose sodium nitrite (SN) on oxygen and glucose deprivation (OGD)-induced endoplasmic reticulum (ER) stress in PC12 cells. The PC12 cells were exposed to 4 h of OGD and treated with 100 mu mol SN. The expression and activity of ER stress markers, including PKR-like endoplasmic reticulum kinase (PERK), transcription factor 6 (ATF6), CCAAT/enhancer binding protein homologous protein (CHOP), as well as caspase-12 and -3, were detected by immunoblotting assay. Fluorescence staining was used to detect the levels of reactive oxygen species (ROS) and Ca2+ release from the ER. Cell viability was also evaluated by MTT assay. It was found that SN significantly inhibited ROS production and Ca2+ release from the ER in OGD-injured PC12 cells. Moreover, ER stress marker expression and cleaved fragments of caspase-3 and -12 in OGD-injured PC12 cells were decreased after SN treatment. These findings were accompanied by a significant increase in cell viability. It seems that SN exerts a neuroprotective effect at least partially through reduction of ROS-mediated ER stress caused by OGD insult.