title: Oxidized low-density lipoprotein induced mouse hippocampal HT-22 cell damage via promoting the shift from autophagy to apoptosis.
abstract: OBJECTIVE
  Although oxidized low-density lipoprotein (ox-LDL) in the brain induces neuronal death, the mechanism underlying the damage effects remains largely unknown. Given that the ultimate outcome of a cell is depended on the balance between autophagy and apoptosis, this study was performed to explore whether ox-LDL induced HT-22 neuronal cell damage via autophagy impairment and apoptosis enhancement.
  
  
  METHODS
  Flow cytometry and transmission electron microscopy (TEM) were used to evaluate changes in cell apoptosis and autophagy, respectively. The protein expression of LC3-II, p62, Bcl-2, and Bax in HT-22 cells was measured by Western bolt analysis.
  
  
  RESULTS
  Our study confirmed that 100 μg/mL of ox-LDL not only promoted TH-22 cell apoptosis, characterized by elevated cell apoptosis rate and Bax protein expression, decreased Bcl-2 protein expression, and damaged cellular ultrastructures, but also impaired autophagy as indicated by the decreased LC3-II levels and the increased p62 levels. Importantly, all of these effects of ox-LDL were significantly aggravated by cotreatment with chloroquine (an inhibitor of autophagy flux). In contrast, cotreatment with rapamycin (an inducer of autophagy) remarkably reversed these effects of ox-LDL.
  
  
  CONCLUSIONS
  Taken together, our results indicated that ox-LDL-induced shift from autophagy to apoptosis contributes to HT-22 cell damage.
authors.affiliation: Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, China.
authors.forename: Hong-Feng
authors.identifier: http://orcid.org/0000-0002-4062-7057
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of Neurology of the First Affiliated Hospital, University of South China, Hengyang, China.
authors.forename: Hai-Zhe
authors.initials: HZ
authors.lastname: Li
authors.affiliation: Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, China.
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Xie
authors.affiliation: Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Tang
authors.affiliation: Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
authors.affiliation: Department of Neurology of the First Affiliated Hospital, University of South China, Hengyang, China.
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Nie
authors.affiliation: Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, China.
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D018501:Antirheumatic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006624:Hippocampus / Q000166:cytology; D008077:Lipoproteins, LDL / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000071456:Sequestosome-1 Protein / Q000378:metabolism; D012844:Sincalide / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D017304:Annexin A5; D018501:Antirheumatic Agents; D051017:Apoptosis Regulatory Proteins; D008077:Lipoproteins, LDL; D019253:Proto-Oncogene Proteins c-bcl-2; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D051028:bcl-2-Associated X Protein; C099252:oxidized low density lipoprotein; D002738:Chloroquine; D012844:Sincalide; D020123:Sirolimus
keywords: HT-22 cell; apoptosis; autophagy; cell damage; oxidized low-density lipoprotein