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Autophagy protects PC12 cells against deoxynivalenol toxicity via the Class III PI3K/beclin 1/Bcl-2 pathway.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-01-12 , DOI: 10.1002/jcp.29433 Xichun Wang 1 , Yunjing Jiang 1 , Lei Zhu 1 , Li Cao 1 , Wei Xu 1 , Sajid Ur Rahman 1 , Shibin Feng 1 , Yu Li 1 , Jinjie Wu 1
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-01-12 , DOI: 10.1002/jcp.29433 Xichun Wang 1 , Yunjing Jiang 1 , Lei Zhu 1 , Li Cao 1 , Wei Xu 1 , Sajid Ur Rahman 1 , Shibin Feng 1 , Yu Li 1 , Jinjie Wu 1
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Deoxynivalenol (DON) is a major mycotoxin from the trichothecene family of mycotoxins produced by Fusarium fungi. It can cause a variety of adverse effects on human and farm animal health. Here, we determined the effect of DON on the Class III phosphatidylinositol 3‐kinase (PIK3C3)/beclin 1/B cell lymphoma‐2 (Bcl‐2) pathway in PC12 cells and the relationship between autophagy and apoptosis. The effects of DON were evaluated based on the apoptosis ratio; the typical indicators of autophagy, including cellular morphology, acridine orange‐ and monodansylcadaverine‐labeled vacuoles, green fluorescent protein–microtubule associated protein 1 light chain 3 (LC3) localization, and LC3 immunofluorescence; and the expression of key autophagy‐related genes and proteins, that is, PIK3C3, beclin 1, Bcl‐2, LC3, and p62. The relationship between autophagy and apoptosis was analyzed by western blot analysis and flow cytometry. DON‐induced PC12 cell morphological changes and autophagy significantly. PIK3C3, beclin 1, and LC3 increased in tandem with the DON concentration used; Bcl‐2 and p62 expression decreased as DON concentrations increased. Moreover, the PIK3C3/beclin 1/Bcl‐2 signaling pathway played a role in DON‐induced autophagy. Our findings suggest that DON can induce autophagy by activating the PIK3C3/beclin 1/Bcl‐2 signaling pathway and that autophagy may play a positive role in reducing DON‐induced apoptosis.
中文翻译：
自噬通过III类PI3K / beclin 1 / Bcl-2途径保护PC12细胞免受脱氧雪腐酚的毒性。
脱氧雪腐烯醇（DON）是镰刀菌属（Fusarium）生产的霉菌毒素的单端孢菌素家族的一种主要霉菌毒素菌类。它可能对人类和农场动物的健康造成各种不利影响。在这里，我们确定了DON对PC12细胞中III类磷脂酰肌醇3激酶（PIK3C3）/ beclin 1 / B细胞淋巴瘤2（Bcl-2）途径的影响以及自噬与凋亡的关系。根据细胞凋亡率评估DON的作用。自噬的典型指标包括细胞形态，a啶橙和单丹酰尸胺标记的液泡，绿色荧光蛋白-微管相关蛋白1轻链3（LC3）定位和LC3免疫荧光。以及与自噬相关的关键基因和蛋白质的表达，即PIK3C3，beclin 1，Bcl-2，LC3和p62。通过蛋白质印迹分析和流式细胞仪分析自噬与凋亡的关系。DON诱导的PC12细胞形态变化和自噬显着。PIK3C3，beclin 1和LC3随所用DON浓度的增加而增加。Bcl-2和p62表达随DON浓度增加而降低。此外，PIK3C3 / beclin 1 / Bcl-2信号通路在DON诱导的自噬中发挥了作用。我们的发现表明DON可以通过激活PIK3C3 / beclin 1 / Bcl-2信号通路来诱导自噬，并且自噬可能在减少DON诱导的细胞凋亡中发挥积极作用。
更新日期：2020-01-12
中文翻译：
自噬通过III类PI3K / beclin 1 / Bcl-2途径保护PC12细胞免受脱氧雪腐酚的毒性。
脱氧雪腐烯醇（DON）是镰刀菌属（Fusarium）生产的霉菌毒素的单端孢菌素家族的一种主要霉菌毒素菌类。它可能对人类和农场动物的健康造成各种不利影响。在这里，我们确定了DON对PC12细胞中III类磷脂酰肌醇3激酶（PIK3C3）/ beclin 1 / B细胞淋巴瘤2（Bcl-2）途径的影响以及自噬与凋亡的关系。根据细胞凋亡率评估DON的作用。自噬的典型指标包括细胞形态，a啶橙和单丹酰尸胺标记的液泡，绿色荧光蛋白-微管相关蛋白1轻链3（LC3）定位和LC3免疫荧光。以及与自噬相关的关键基因和蛋白质的表达，即PIK3C3，beclin 1，Bcl-2，LC3和p62。通过蛋白质印迹分析和流式细胞仪分析自噬与凋亡的关系。DON诱导的PC12细胞形态变化和自噬显着。PIK3C3，beclin 1和LC3随所用DON浓度的增加而增加。Bcl-2和p62表达随DON浓度增加而降低。此外，PIK3C3 / beclin 1 / Bcl-2信号通路在DON诱导的自噬中发挥了作用。我们的发现表明DON可以通过激活PIK3C3 / beclin 1 / Bcl-2信号通路来诱导自噬，并且自噬可能在减少DON诱导的细胞凋亡中发挥积极作用。
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