کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11010650 | 1807145 | 2018 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ochratoxin A induces cytoprotective autophagy via blocking AKT/mTOR signaling pathway in PK-15â¯cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
دانش تغذیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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 2.0-8.0â¯Î¼M could increase cytotoxicity of PK-15â¯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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Food and Chemical Toxicology - Volume 122, December 2018, Pages 120-131
Journal: Food and Chemical Toxicology - Volume 122, December 2018, Pages 120-131
نویسندگان
Gang Qian, Dandan Liu, Lili Hou, Mohammed Hamid, Xingxiang Chen, Fang Gan, Suquan Song, Kehe Huang,