title: The cytotoxicity of 27-hydroxycholesterol in co-cultured SH-SY5Y cells and C6 cells.
abstract: BACKGROUND
  Diverse physiological and pathological functions of 27-hydroxycholesterol (27-OHC) were proved. However, cytotoxicity and potential influence of 27-OHC on cholesterol metabolism in neurons are unclear.
  
  
  METHODS
  In the vitro co-culture system, SH-SY5Y cells and C6 cells were applied to explore the potential cytotoxicity of 27-OHC. MTT assay was used to detect the cell proliferation. Cell vitality was measured by using the Annexin-FITC/PI test. Immunofluorescence technique was applied to observe the changes of mitochondria membrane potential. The expression of mRNA and protein (including SREBP-1, HMGCR, LXR-α, ABCA1) were measured by real-time PCR and western blot method respectively.
  
  
  RESULTS
  27-OHC induced apoptosis in co-cultured SH-SY5Y cells and C6 cells. 27-OHC treatment significantly inhibited cell viability and proliferation (p<0.05). Compared with control group, 27-OHC caused the reduction of mitochondrial membrane potential (p<0.05). Additionally, the mRNA and protein expression of cholesterol synthesis-related factors, such as SREBP-1, HMGCR, were down-regulated (p<0.05), while the mRNA and protein expression of cholesterol transport-related factors (LXR-α, ABCA1) were up-regulated (p<0.05).
  
  
  CONCLUSIONS
  Cytotoxicity and cholesterol metabolism disorder induced by 27-OHC may contribute to the pathogenesis of neurodegenerative disease.
authors: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors: Hui
authors: H
authors: Wang
authors: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors: Linhong
authors: L
authors: Yuan
authors: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors: Weiwei
authors: W
authors: Ma
authors: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors: Jing
authors: J
authors: Han
authors: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors: Yanhui
authors: Y
authors: Lu
authors: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors: Lingli
authors: L
authors: Feng
authors: School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: xiaor22@ccmu.edu.cn.
authors: Rong
authors: R
authors: Xiao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D018920:Coculture Techniques; D003603:Cytotoxins / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003603:Cytotoxins; D006888:Hydroxycholesterols; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C076996:27-hydroxycholesterol; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases
keywords: 27-Hydroxycholesterol; Cholesterol synthesis; Cholesterol transport; Cytotoxic