氯化镧对大鼠星形胶质细胞内质网应激及凋亡的影响

发布时间：2018-04-24 03:07

本文选题：氯化镧 + GRP-　；参考：《环境与健康杂志》2015年08期

【摘要】：目的观察氯化镧(LaCl3)对大鼠大脑皮质星形胶质细胞(Ast)中葡糖调节蛋白-94(GRP-94)、蛋白激酶R样内质网激酶(PERK)、生长阻滞和DNA损伤诱导蛋白153(GADD153)、半胱天冬蛋白酶-12(caspase-12)表达的影响。方法分别用0、0.25、0.5、1.0 mmol/L LaCl3作用Ast细胞24 h,再以四甲基偶氮唑盐法检测Ast细胞活力,以流式细胞仪检测Ast细胞凋亡,以Western blotting法检测Ast细胞GRP-94、PERK、磷酸化PERK(pPERK)、GADD153和caspase-12的水平。结果 0.25、0.5、1.0 mmol/L LaCl3染毒后,Ast细胞活力降低,Ast细胞凋亡升高,均呈剂量-效应关系,差异均有统计学意义(P0.05)。0.25、0.5、1.0 mmol/L LaCl3染毒组Ast细胞的GRP-94、pPERK、GADD153、caspase-12水平均高于对照组,其中1.0 mmol/L LaCl3染毒组上述指标分别为对照组的3.10、5.25、2.73、3.14倍,差异均有统计学意义(P0.05)。结论 GRP-94、pPERK、GADD153和caspase-12表达上调使凋亡异常增多,其可能是LaCl3对Ast细胞产生毒作用的机制之一。
[Abstract]:Objective to investigate the effects of lanthanum chloride (LaCl3) on the expression of glucose-regulated protein (-94) GRP-94, protein kinase R-like endoplasmic reticulum kinase (PERKN), growth arrest and DNA damage inducible protein 153 (GADD153), and cysteinase (caspase-12) in rat cerebral cortex astrocytes. Methods Ast cells were treated with 0.25 mmol/L LaCl3 for 24 h, then the viability of Ast cells was detected by tetramethylazolium method, apoptosis of Ast cells was detected by flow cytometry, the levels of GRP-94 PERK, phosphorylated PERKPERK153 and caspase-12 were detected by Western blotting assay. Results after 0. 5 mmol/L LaCl3 exposure, the activity of Ast cells decreased the apoptosis of AST cells in a dose-effect relationship, and the difference was statistically significant in the Ast cells exposed to 0. 05 and 0. 25 mmol/L LaCl3. The level of GRP-94 pPERKN GADD153 caspase-12 was higher than that of the control group, and the expression of GADD153 caspase-12 in the Ast cells was significantly higher than that in the control group (P < 0. 05, P < 0. 05, P = 0. 05, P = 0. 05, P < 0. 05). The above indexes in 1.0 mmol/L LaCl3 group were 3.14 times higher than those in control group (P 0.05). Conclusion the upregulation of GADD153 and caspase-12 expression of GRP-94pPERKT may lead to the abnormal increase of apoptosis, which may be one of the mechanisms of the toxic effect of LaCl3 on Ast cells.
【作者单位】：中国医科大学公共卫生学院卫生毒理学教研室;
【基金】：国家自然科学基金(81373024;81273117)
【分类号】：R114

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