title: Nano-TiO2induces autophagy to protect against cell death through antioxidative mechanism in podocytes.
abstract: 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-TiO2induced authophagy. Besides that, whether autophagy could protect podocytes from the damage induced by nano-TiO2and its mechanism was also investigated. Western blot assay and acridine orange staining presented that nano-TiO2significantly 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-TiO2induces 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-TiO2in podocytes.
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Yin
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China.
authors.forename: Zhigui
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*
chemical_list: D000975:Antioxidants; C009495:titanium dioxide; C025946:3-methyladenine; D014025:Titanium; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000225:Adenine; D020123:Sirolimus
keywords: AMPK; Antioxidative effect; Autophagy flux; Podocytes; Titanium dioxide nanoparticles; mTOR