| 刘录山,邓懿铭,李清.缺氧通过HIF-1α/PCSK9信号途径诱导神经细胞凋亡.[J].中南医学科学杂志.,2021,(4):373-378. |
| 缺氧通过HIF-1α/PCSK9信号途径诱导神经细胞凋亡 |
| Hypoxia induces neuronal apoptosis through HIF-1α/PCSK9 signaling pathway |
| 投稿时间：2021-03-04 修订日期：2021-04-23 |
| DOI：10.15972/j.cnki.43-1509/r.2021.04.001 |
| 中文关键词: 前蛋白转化酶枯草溶菌素9 缺氧诱导因子-1α 凋亡 缺氧 缺氧缺血性脑损伤 |
| 英文关键词:PCSK9 HIF-1α apoptosis hypoxia ischemic brain injury |
| 基金项目:国家自然科学基金(81370376)；湖南省自然科学基金(2018JJ2343) |
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| 中文摘要: |
| 目的研究缺氧是否通过上调缺氧诱导因子1α(HIF-1α)水平而调控前蛋白转化酶枯草溶菌素9(PCSK9)表达并诱导神经细胞凋亡。 方法分别用0、125、250、500 μmol/L氯化钴(CoCl2)处理PC12细胞,蛋白印迹法检测其PCSK9及HIF-1α表达；Hoechst33258核染色及流式细胞术检测CoCl2对PC12细胞凋亡的影响。用250 μmol/L CoCl2处理PC12细胞0、6、12、24 h,蛋白印迹法检测其PCSK9及HIF-1α表达。不同浓度HIF-1α激动剂二甲基乙二酰基甘氨酸(DMOG)或HIF-1α抑制剂利非西呱(YC-1)处理PC12细胞24 h,检测PCSK9、HIF-1α、胱天蛋白酶3(Caspase-3)、Caspase-9的表达及对PC12细胞凋亡的影响。PC12细胞经PCSK9 siRNA转染后与250 μmol/L CoCl2孵育,检测对PC12细胞凋亡的影响及PCSK9、HIF-1α、Caspase-3、Caspase-9蛋白的表达。 结果PCSK9、HIF-1α的表达及细胞凋亡程度呈CoCl2浓度与时间依赖性增高。PC12细胞中HIF-1α和PCSK9的表达呈DMOG浓度依赖性增高,Caspase-3、Caspase-9表达及PC12细胞凋亡率呈DMOG浓度依赖性降低；PC12细胞中HIF-1α和PCSK9的表达呈YC-1浓度依赖性降低,Caspase-3、Caspase-9表达及PC12细胞凋亡率呈YC-1浓度依赖性升高。与空白组及无义RNA组比较,PCSK9 siRNA转染组Caspase-3、Caspase-9表达减少,凋亡程度降低。 结论细胞缺氧状态下HIF-1α水平的增高能上调PCSK9表达并调控神经细胞凋亡。 |
| 英文摘要: |
| To unravel if hypoxia elevates the expression of proprotein convertase subtilisin-kexin type 9(PCSK9) by up-regulating expression of hypoxia-induced factor-1 alpha (HIF-1α) to mediate neuronal apoptosis. Methods PC12 cells were treated with 0,125, 250 and 500 μmol/L CoCl2, respectively, and the expression of PCSK9 and HIF-1α were detected by western blot. Hoechst33258 nuclear staining and flow cytometry were used to detect the effect of CoCl2 on PC12 cell apoptosis. PC12 cells were treated with 250 μmol/L CoCl2 for 0,6, 12 and 24 h, and the expression of PCSK9 and HIF-1α were detected by western blot. PC12 cells were treated with different concentrations of HIF-1α agonist dimethylglycoglycine (DMOG) or HIF-1α inhibitor rifeciperum (YC-1) for 24 h, and the expression of PCSK9, HIF-1α, Caspase-3 and Caspase-9 and their effects on apoptosis of PC12 cells were detected. PC12 cells were transfected with PCSK9 siRNA and incubated with 250 μmol/L CoCl2 to detect the effect of PCSK9 apoptosis and the expression of PCSK9, HIF-1α, Caspase-3 and Caspase-9 proteins. Results Expression of PCSK9 and HIF-1α and the degree of apoptosis increased in a time - dependent manner with the concentration of CoCl2. Expression of HIF-1α and PCSK9 in PC12 cells increased in a DMOG concentration-dependent manner, while the expression of Caspase-3 and Caspase-9 and the apoptosis rate of PC12 cells decreased in a DMOG concentration-dependent manner. Expression of HIF-1α and PCSK9 in PC12 cells decreased in a YC-1 concentration-dependent manner, while the expression of Caspase-3 and Caspase-9 and the apoptosis rate of PC12 cells increased in a YC-1 concentration-dependent manner. Compared with blank group and meaningless RNA group, the expression of Caspase-3 and Caspase-9 in PCSK9 siRNA transfection group decreased, and the degree of apoptosis decreased. ConclusionHypoxia increases the level of HIF-1α and promotes the expression of PCSK9 to regulate neuronal apoptosis. |
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