Ochratoxin A induces cytoprotective autophagy via blocking AKT/mTOR signaling pathway in PK-15 cells

被引:19
作者
Qian, Gang [1 ,2 ,3 ]
Liu, Dandan [1 ,2 ]
Hou, Lili [1 ,2 ]
Hamid, Mohammed [1 ,2 ]
Chen, Xingxiang [1 ,2 ]
Gan, Fang [1 ,2 ]
Song, Suquan [1 ]
Huang, Kehe [1 ,2 ]
机构
[1] Nanjing Agr Univ, Coll Vet Med, Nanjing 210095, Jiangsu, Peoples R China
[2] Nanjing Agr Univ, Inst Nutr & Metab Disorders Domest Anim & Fowls, Nanjing 210095, Jiangsu, Peoples R China
[3] Jinling Inst Technol, Dept Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Ochratoxin A; Nephrotoxicity; AKT/mTOR; Autophagy; Apoptosis; KIDNEY PK15 CELLS; CANCER-CELLS; INDUCED APOPTOSIS; OXIDATIVE STRESS; POTENTIAL ROLE; IN-VITRO; ACTIVATION; DEATH; NEPHROTOXICITY; MTOR;
D O I
10.1016/j.fct.2018.09.070
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Ochratoxin A (OTA) could cause a variety of toxicological effects especially nephrotoxicity in animals and humans. Autophagy is a highly conserved metabolic process that plays an important role in the maintenance of cellular homeostasis under stress. However, the role of autophagy in OTA-induced nephrotoxicity is unknown. In the present study, we demonstrated that OTA treatment at 2.0-8.0 mu M could increase cytotoxicity of PK-15 cells by inducing apoptosis as shown by the increased Annexin V/PI staining, increased caspase-3 and PARP cleavage and increased apoptotic nuclei. Meantime, autophagy was triggered when OTA was administrated, as indicated by markedly increased expressions of LC3-II, ATG5 and Beclin-1, accumulation of GFP-LC3 dots and increased double- or single-membrane vesicles. OTA treatment decreased p-AKT and p-mTOR activities, and OTA-induced autophagy was inhibited when insulin was applied. Furthermore, OTA treatments with autophagy inhibitors (3-methyladenine or chloroquine) or knockdown of autophagy-related genes (ATG5 or Beclin-1) resulted in significantly reduced autophagy level and enhanced cytotoxicity. In conclusion, OTA induces cytoprotective autophagy against its cytotoxicity and inactivation of AKT/mTOR axis plays a critical role in autophagy induction.
引用
收藏
页码:120 / 131
页数:12
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