title: Farrerol regulates occludin expression in hydrogen peroxide-induced EA.hy926 cells by modulating ERK1/2 activity.
abstract: Endothelial tight junction is a crucial intracellular junctional structure that controls paracellular permeability across vascular endothelium. Oxidative stress-mediated elevation in endothelial permeability is associated with pathogenesis of several cardiovascular diseases. In the present research, the regulation of farrerol on occludin, a transmembrane proteins associated with endothelial tight junction, was investigated in hydrogen peroxide-induced human endothelium-derived EA.hy926 cells. Western blot analysis demonstrated that H2O2 exposure caused a significant decrease in occludin expression, but had little effect on ZO-1 expression, and the decrease of occludin expression was significantly attenuated by farrerol in a dose-dependent manner. Meanwhile, immunofluorescent staining assay also demonstrated that the loss of occludin expression induced by H2O2 exposure was restored by farrerol pretreatment. Further investigations showed that farrerol prevented H2O2-induced activation of extracellular signal-regulated kinase (ERK) 1/2 in a dose-dependent manner. The use of U0126, a specific inhibitor of MEK1/2, proved that H2O2-induced decrease of occludin in EA.hy926 cells was likely associated with activation of ERK1/2, which indicated that the regulation of farrerol on occludin expression in H2O2-induced EA.hy926 cells was likely related to the modulation of ERK1/2 activation. In conclusion, the present study demonstrates for the first time that farrerol has potential effects on oxidative stress-induced endothelial tight junction disruption and suggests that farrerol is a potential candidate for the intervention of endothelial permeability-associated cardiovascular diseases.
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China; School of Public Health Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China.
authors.forename: Jiankuan
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China.
authors.forename: Chengxiao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: School of Public Health Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China; School of Public Health Science, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, China. Electronic address: sxlqs2012@163.com.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Li
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D062793:Occludin / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D002867:Chromones; D062793:Occludin; C015881:farrerol; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: EA.hy926 cells; Extracellular signal-regulated kinase (ERK) 1/2; Farrerol; Occludin; Tight junction