Hernández-Zimbrón Luis Fernando, Rivas-Arancibia Selva
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico.
Biomed Res Int. 2016;2016:2125643. doi: 10.1155/2016/2125643. Epub 2016 Jun 5.
Oxidative stress is a risk factor for Alzheimer's disease and it is currently accepted that oxidative damage precedes the overproduction of A42 peptide. We have reported that ozone causes oxidative stress inducing neurodegeneration in the brain of rats. It is associated with A42 overproduction and intracellular accumulation in hippocampus. Organelles like mitochondria, intracellular membranes, and endoplasmic reticulum have been identified as sites of A42 production and accumulation affecting cellular metabolism. However whether ozone exposure induces overproduction and/or accumulation of A42 in endoplasmic reticulum has not been studied. We evaluated this effect in the endoplasmic reticulum of hippocampal cells of rats exposed chronically to low doses of ozone (0.25 ppm) at 7, 15, 30, 60, and 90 days. The effect of the presence of A42 in endoplasmic reticulum was analyzed evaluating the expression of the chaperone Syntaxin 5. Our results show an accumulation of A42 peptide in this organelle. It was observed by immunofluorescence and by WB in endoplasmic fractions from hippocampal cells of rats at 60 and 90 days of treatment. Significant overexpression of the chaperone Syntaxin 5 at 60 and 90 days of treatment was observed ((⁎) P < 0.05). These results indicate that the exposure to environmental pollutants could be involved as a risk factor for neurodegenerative processes.
氧化应激是阿尔茨海默病的一个风险因素，目前人们普遍认为氧化损伤先于A42肽的过量产生。我们曾报道，臭氧会引起氧化应激，导致大鼠大脑神经退行性变。这与海马体中A42的过量产生和细胞内积累有关。线粒体、细胞内膜和内质网等细胞器已被确定为影响细胞代谢的A42产生和积累的部位。然而，臭氧暴露是否会在内质网中诱导A42的过量产生和/或积累尚未得到研究。我们评估了长期暴露于低剂量臭氧（0.25 ppm）7天、15天、30天、60天和90天的大鼠海马体细胞内质网中的这种效应。通过评估伴侣蛋白Syntaxin 5的表达，分析了内质网中A42存在的影响。我们的结果显示该细胞器中存在A42肽的积累。在治疗60天和90天的大鼠海马体细胞内质网部分，通过免疫荧光和蛋白质印迹法观察到了这种积累。在治疗60天和90天时观察到伴侣蛋白Syntaxin 5有显著的过表达（（⁎）P < 0.05）。这些结果表明，暴露于环境污染物可能作为神经退行性过程的一个风险因素。
