Abstract
Purpose2,3-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).MethodsHL-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.ResultsWe 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.ConclusionsThese 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.
Highlights
Obstructive sleep apnea (OSA) is caused by recurrent closure of the upper airway during sleep, which leads to repetitive intermittent hypoxia (IH) [1]
1 Department of Endocrinology, The Fifth Affiliated Hospital of Zhengzhou University, No 3 Rehabilitation Street, Zhengzhou 450052, People’s Republic of China. These findings suggest that Oxidosqualene cyclase (OSC) are involved in IH-induced hepatic cell injury
As compared with exposure to normoxia, HL-02 cells treated with IH had reduced cell proliferation as assessed by the Cell Counting Kit-8 (CCK-8) assay (Fig. 1a)
Summary
Obstructive sleep apnea (OSA) is caused by recurrent closure of the upper airway during sleep, which leads to repetitive intermittent hypoxia (IH) [1]. OSA is a common disorder, present in 2 % of women and 4 % of men in the population [2, 3]. Obesity is a major risk factor for OSA, and prevalence of OSA exceeds 50 % in obese men [4, 5]. OSA has been associated with an increased risk of hypertension, type 2 diabetes, dyslipidemia, and atherosclerosis, independent of underlying obesity [6,7,8,9]. Accumulating evidence showed that OSA is associated with elevation in liver enzymes and biopsy evidence of liver injury. The severity of liver injury in patients with OSA directly correlates with the severity of the hypoxic insult [10,11,12,13]
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