title: 2,3-Oxidosqualene cyclase protects liver cells from the injury of intermittent hypoxia by regulating lipid metabolism.
abstract: OBJECTIVE
  2,3-Oxidosqualene cyclase (OSC), an important enzyme of cholesterol biosynthesis, catalyzes the highly selective cyclization of 2,3-monoepoxysqualene to lanosterol. Intermittent hypoxia (IH) is a hallmark feature in obstructive sleep apnea (OSA) which is increasingly recognized as an independent risk factor for liver injury. The aim of this study was to determine the effect of IH on OSC expression and evaluate the role of OSC in the IH-induced apoptosis in hepatic cell line human liver cell (HL-02).
  
  
  METHODS
  HL-02 cells were exposed to normoxia or IH. Cell Counting Kit-8 (CCK-8) assay was used to value cell proliferation, and flow cytometry was used to determine cell apoptosis. The expression of OSC messenger RNA (mRNA) was evaluated by quantitative real-time PCR, and the expression of OSC protein was determined by Western blot. To further investigate the function of OSC in IH-induced apoptosis, oxidosqualene cyclase-enhanced green fluorescence protein (OSC-EGFP) plasmid was constructed to over-express OSC protein. Triglyceride content in HL-02 cells was analyzed by oil red staining or Triglyceride Quantification Kit.
  
  
  RESULTS
  We found that IH inhibited HL-02 cell proliferation and accelerated cell apoptosis. IH decreased OSC expression, and over-expression of OSC could protect HL-02 cells against the IH-induced hepatic cell injury. Moreover, over-expression of OSC could attenuate IH-induced cellular triglyceride accumulation.
  
  
  CONCLUSIONS
  These findings suggest that OSC are involved in IH-induced hepatic cell injury. These results may contribute to the further understanding of the mechanism underlying the liver injury in OSA patients.
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China.
authors: Yue-Qiao
authors: YQ
authors: Zhen
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China.
authors: Yu-Min
authors: YM
authors: Wu
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China.
authors: Yan-Hong
authors: YH
authors: Sang
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China.
authors: Yan
authors: Y
authors: Wang
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China.
authors: Qiu-Yan
authors: QY
authors: Song
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China.
authors: Ling
authors: L
authors: Yu
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China.
authors: Xiao-Juan
authors: XJ
authors: Rao
authors: Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Rehabilitation Street, Zhengzhou, 450052, People's Republic of China. 2849657110@qq.com.
authors: Rui-Hong
authors: RH
authors: Dong
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D019751:Intramolecular Transferases / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D013185:Squalene / Q000031:analogs & derivatives* / Q000097:blood; D014280:Triglycerides / Q000097:blood
chemical_list: C002821:2,3-oxidosqualene; D014280:Triglycerides; D013185:Squalene; D002784:Cholesterol; D019751:Intramolecular Transferases; C021924:lanosterol synthase
keywords: 2,3-Oxidosqualene cyclase; Intermittent hypoxia; Obstructive sleep apnea; Triglyceride