期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 122, 期 -, 页码 120-131出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2018.09.070
关键词
Ochratoxin A; Nephrotoxicity; AKT/mTOR; Autophagy; Apoptosis
资金
- National Natural Science Foundation of China [31772811, 31472253, 31472252]
- Fundamental Research Funds for the Central Universities [Y0201500198]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (Jiangsu, China)
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据