A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells
This study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by re...
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| Format: | Article |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00768/full |
| _version_ | 1818933286989201408 |
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| author | Ziyin Lu Ziyin Lu Chunli Chen Zhiyong Wu Yusong Miao Ishfaq Muhammad Liangjun Ding Erjie Tian Wanjun Hu Huilin Ni Rui Li Bo Wang Jichang Li Jichang Li |
| author_facet | Ziyin Lu Ziyin Lu Chunli Chen Zhiyong Wu Yusong Miao Ishfaq Muhammad Liangjun Ding Erjie Tian Wanjun Hu Huilin Ni Rui Li Bo Wang Jichang Li Jichang Li |
| author_sort | Ziyin Lu |
| collection | DOAJ |
| description | This study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by real-time PCR and western blot, fluorescence/immunofluorescence microscopy, and electron microscopy. The results showed that silencing of p53 leads to down-regulation of Atg5 and beclin1 for 12 h while up-regulation at 24 h and up-regulation of p62 noted. The ratio of LC3-II/I and autophagic vacuoles were significantly increased at 24 h, but autophagy flux was blocked. The cleavage of caspase3 and PARP (poly ADP-ribose polymerase) were enhanced, while PC-12-sip53 cells exposed to 3-MA showed down-regulation of apoptosis. By contrast, the expression of autophagy-related genes and protein reduced in p53 overexpressing cells following a time dependent manner. Meanwhile, there was an increase in the expression of activated caspase3 and PARP, condensed and fragmented nuclei were evident. Conclusively, the data supported that silencing of p53 promotes impaired autophagy, which acts as a pro-apoptotic induction factor in PC-12 cells treated with colistin for 24 h, and overexpression of p53 inhibits autophagy and accelerates apoptosis. Hence, it has been suggested that p53 could not act as a neuro-protective target in colistin-induced neurotoxicity. |
| first_indexed | 2024-12-20T04:45:59Z |
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| id | doaj.art-66ffbe843cfc4c73a53f9e37efd4d967 |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T04:45:59Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-66ffbe843cfc4c73a53f9e37efd4d9672022-12-21T19:52:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-10-01810.3389/fphar.2017.00768301779A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 CellsZiyin Lu0Ziyin Lu1Chunli Chen2Zhiyong Wu3Yusong Miao4Ishfaq Muhammad5Liangjun Ding6Erjie Tian7Wanjun Hu8Huilin Ni9Rui Li10Bo Wang11Jichang Li12Jichang Li13Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Animal Production, College of Life Engineering, Shenyang Institute of Technology, Fushun, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaDepartment of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Northeast Agricultural University, Harbin, ChinaHeilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin, ChinaThis study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by real-time PCR and western blot, fluorescence/immunofluorescence microscopy, and electron microscopy. The results showed that silencing of p53 leads to down-regulation of Atg5 and beclin1 for 12 h while up-regulation at 24 h and up-regulation of p62 noted. The ratio of LC3-II/I and autophagic vacuoles were significantly increased at 24 h, but autophagy flux was blocked. The cleavage of caspase3 and PARP (poly ADP-ribose polymerase) were enhanced, while PC-12-sip53 cells exposed to 3-MA showed down-regulation of apoptosis. By contrast, the expression of autophagy-related genes and protein reduced in p53 overexpressing cells following a time dependent manner. Meanwhile, there was an increase in the expression of activated caspase3 and PARP, condensed and fragmented nuclei were evident. Conclusively, the data supported that silencing of p53 promotes impaired autophagy, which acts as a pro-apoptotic induction factor in PC-12 cells treated with colistin for 24 h, and overexpression of p53 inhibits autophagy and accelerates apoptosis. Hence, it has been suggested that p53 could not act as a neuro-protective target in colistin-induced neurotoxicity.http://journal.frontiersin.org/article/10.3389/fphar.2017.00768/fullcolistinautophagyp53PC-12 cellsapoptosis |
| spellingShingle | Ziyin Lu Ziyin Lu Chunli Chen Zhiyong Wu Yusong Miao Ishfaq Muhammad Liangjun Ding Erjie Tian Wanjun Hu Huilin Ni Rui Li Bo Wang Jichang Li Jichang Li A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells Frontiers in Pharmacology colistin autophagy p53 PC-12 cells apoptosis |
| title | A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells |
| title_full | A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells |
| title_fullStr | A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells |
| title_full_unstemmed | A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells |
| title_short | A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells |
| title_sort | dual role of p53 in regulating colistin induced autophagy in pc 12 cells |
| topic | colistin autophagy p53 PC-12 cells apoptosis |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00768/full |
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