Nano-TiO_lus-plus">2 induces autophagy to protect against cell death through antioxidative mechanism in podocytes

详细信息    查看全文

• 作者：Xiaochen Zhang ; Hongqiang Yin ; Zhigui Li ; Tao Zhang…
• 关键词：AMPK ; Antioxidative effect ; Autophagy flux ; mTOR ; Podocytes ; Titanium dioxide nanoparticles
• 刊名：Cell Biology and Toxicology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：32
• 期：6
• 页码：513-527
• 全文大小：2,878 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Pharmacology and Toxicology
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-6822
• 卷排序：32

文摘

Autophagy is a cellular pathway involved in degradation of damaged organelles and proteins in order to keep cellular homeostasis. It plays vital role in podocytes. Titanium dioxide nanoparticles (nano-TiO₂) are known to induce autophagy in cells, but little has been reported about the mechanism of this process in podocytes and the role of autophagy in podocyte death. In the present study, we examined how nano-TiO₂ induced authophagy. Besides that, whether autophagy could protect podocytes from the damage induced by nano-TiO₂ and its mechanism was also investigated. Western blot assay and acridine orange staining presented that nano-TiO₂ significantly enhanced autophagy flux in podocytes. In addition, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were involved in such process. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that upregulated level of autophagy induced by rapamycin in high concentration nano-TiO₂-treated podocytes could significantly reduce the level of oxidative stress and alleviate podocyte death. Downregulating the level of autophagy with 3-methyladenine had the opposite effects. These findings indicate that nano-TiO₂ induces autophagy through activating AMPK to inhibit mTOR in podocytes, and such autophagy plays a protecting role against oxidative stress on the cell proliferation. Changing autophagy level may become a new treatment strategy to relieve the damage induced by nano-TiO₂ in podocytes.