title: Colistin-induced apoptosis in PC12 cells: involvement of the mitochondrial apoptotic and death receptor pathways.
abstract: Colistin, a cyclic cationic polypeptide antibiotic that is used to treat infections, may cause neurotoxicity. However, whether colistin can induce apoptosis and the precise mechanism of apoptosis involved in PC12 cells remains to be determined. The aim of the present study was to determine reactive oxygen species (ROS) level and DNA damage, as well as apoptotic factors such as p53, cytochrome c, Bax, Bcl-2, Fas, Fas-L and caspase family via western blotting in PC12 cells treated with colistin sulfate. The results showed that colistin sulfate increased ROS levels significantly. An increase of ROS levels induces the release of cytochrome c and DNA damage. DNA damage can activate p53, which leads to the upregulation of Bax and downregulation of Bcl-2. The imbalance of Bax/Bcl-2 promotes additional release of cytochrome c. The release of cytochrome c contributes to the activation of caspase-9 and the subsequent activation of caspase-3. An increase of Fas and Fas-L induced the activation of caspase-8 leading to the activation of caspases-3, the latter induces apoptosis. Therefore, these results demonstrate that the apoptotic pathway of colistin-induced apoptosis in PC12 cells is involved in both the mitochondrial and death receptor pathway.
authors.affiliation: College of Animal Husbandry and Veterinary Medicine, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
authors.forename: Jichang
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Animal Husbandry and Veterinary Medicine, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Tiezhong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: College of Animal Husbandry and Veterinary Medicine, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wang
authors.affiliation: Scientific Research Department, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Animal Husbandry and Veterinary Medicine, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003091:Colistin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D003091:Colistin