Autophagy protects PC12 cells against deoxynivalenol toxicity via the Class III PI3K/beclin 1/Bcl‐2 pathway

• Published in: Journal of cellular physiology 2020-11, Vol.235 (11), p.7803-7815
• Main Authors: Wang, Xichun, Jiang, Yunjing, Zhu, Lei, Cao, Li, Xu, Wei, Rahman, Sajid ur, Feng, Shibin, Li, Yu, Wu, Jinjie
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Acridine orange; Animal health; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Autophagy; Autophagy - drug effects; Autophagy - physiology; Bcl-2 protein; Beclin-1 - metabolism; class III PI3K/beclin 1/Bcl‐2 pathway; Deoxynivalenol; Flow cytometry; Fluorescence; Fungi; Green fluorescent protein; Immunofluorescence; Kinases; Localization; Lymphoma; Morphology; Mycotoxins; PC12 Cells; Phagocytosis; Pheochromocytoma cells; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; Signaling; Toxicity; Trichothecenes - toxicity; Vacuoles
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29433

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. Our findings suggest that deoxynivalenol (DON) can induce autophagy by activating the class III phosphatidylinositol 3‐kinase/beclin 1/B cell lymphoma‐2 signaling pathway and that autophagy may play a positive role in reducing DON‐induced apoptosis.