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2,3-Oxidosqualene Cyclase Protects Liver Cells From the Injury of Intermittent Hypoxia by Regulating Lipid Metabolism

2,3-Oxidosqualene Cyclase Protects Liver Cells From the Injury of Intermittent Hypoxia by Regulating Lipid Metabolism

Yue-Qiao Zhen, Yu-Min Wu, Yan-Hong Sang, Yan Wang, Qiu-Yan Song, Ling Yu, Xiao-Juan Rao, Rui-Hong Dong

Sleep Breath. 2015 Dec;19(4):1475-81.

PMID: 25855471

Abstract:

Purpose:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP7200262	2,3-Oxidosqualene		7200-26-2	Price

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