RESUMEN
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.
Asunto(s)
Hepatocitos/fisiología , Hipoxia/fisiopatología , Metabolismo de los Lípidos/fisiología , Apnea Obstructiva del Sueño/fisiopatología , Escualeno/análogos & derivados , Apoptosis/fisiología , Línea Celular , Proliferación Celular/fisiología , Colesterol/sangre , Humanos , Transferasas Intramoleculares/fisiología , Factores de Riesgo , Escualeno/sangre , Triglicéridos/sangreRESUMEN
Arsenic toxicity, mobility and bioaccessibility are influenced by its different speciation in soil, which exerts different impacts on the environment. In this study, coal fly ash, dried sludge, ferrous sulfate and broken peanut shell were used as stabilizers to investigate their stabilizing effects on As in soil as well as relationships between pH, soil organic matter content, cation exchange capacity and speciation of soil As. The results showed rise in soil pH, soil organic matter content and residual arsenic content after the addition of stabilizers. Addition of 10% coal fly ash and 10% dried sludge led to the decrease in the content of exchangeable As, carbonate bound As, Fe-Mn oxide bound As, organic bound As by 34.2%, 17.5%, 19.9%, 53.7%, respectively. Addition of ferrous sulfate could preferably stabilize As in soil. When 10% coal fly ash, 10% dried sludge and 1% ferrous sulfate were added concurrently, the decrease in the content of exchangeable As, carbonate bound As, Fe-Mn oxide bound As, organic bound As was 62.3%, 55.2%, 29.6%, 58.2%, respectively, with an increase in residual arsenic content by 8.1%. After the addition of 10% coal fly ash, 10% dried sludge, 1% ferrous sulfate and 1% broken peanut shell, a most conspicuous decrease in the content of exchangeable As by 73.3% was observed. Appropriate application of coal fly ash, dry sludge and ferrous sulfate converted a proportion of exchangeable, carbonate bounded, Fe-Mn bounded, organic bounded As into residual As, which reduced As's toxicity. The rise in pH led to increasing residual As content and decreasing exchangeable As, carbonate bounded As, Fe-Mn bounded As and organic bounded As content, and As was most stable at the approach of neutral condition. The rise in organic matter content led to increasing carbonate bounded As and residual As content and decreasing exchangeable As, Fe-Mn bounded As, organic bounded As content. The rise in cation exchange capacity led to increasing residual As content and decreasing exchangeable As, carbonate bounded As, Fe-Mn bounded As and organic bounded As content.