title: Protective Effect of 2,4',5'-Trihydroxyl-5,2'-dibromo diphenylmethanone, a New Halophenol, against Hydrogen Peroxide-Induced EA.hy926 Cells Injury.
abstract: Vascular endothelial cells produce reactive oxygen species (ROS) during the process of energy metabolism in aerobic respiration. A growing body of evidence indicates that excessive ROS is implicated in the pathogenesis of cardiovascular diseases including atherosclerosis. The newly synthesized halophenol, 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone (TDD), exhibits antioxidative and cytoprotective activities in vitro. In this study, the protective effect of TDD against hydrogen peroxide (H2O2)-induced oxidative injury of EA.hy926 cells was investigated. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide (MTT) assay, while the effect of TDD on the transcription profile of EA.hy926 cells subjected to H2O2-induced oxidative injury was evaluated by microarray analysis. Several signaling pathways, including apoptosis, were significantly associated with TDD. Flow cytometric analysis was used to evaluate anti-apoptotic effect of TDD. Subsequently, RT-PCR and Western blot were used to detect the expressions of the apoptosis-associated protein, Bcl-2 and Bax. Meanwhile the expression of cleaved caspase-3, an executioner of apoptosis, was also detected by Western blot. The results showed that pretreatment of EA.hy926 cells with TDD prevented the decrease of cell viability induced by H2O2, and attenuated H2O2-induced elevation of Bax and cleaved caspase-3 while increased Bcl-2 expressions. In summary, TDD inhibited H2O2-induced oxidative injury of EA.hy926 cells through negative regulation of apoptosis. These findings suggest that TDD is a potential candidate for therapeutic intervention in oxidative stress-associated cardiovascular diseases.
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China. ljg2547@163.com.|School of Public Health Science, Shanxi Medical University, Taiyuan 030001, China. ljg2547@163.com.|Shanxi Key Laboratory of Drug Toxicology and Drug for Radiation Injury, China Institute for Radiation Protection, Taiyuan 030006, China. ljg2547@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China. xiuefeng@163.com.
authors.forename: Xiue
authors.initials: X
authors.lastname: Feng
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China. cpugr@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China. ljg2547@163.com.
authors.forename: Jiankuan
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan 030001, China. sxlqs2012@163.com.|School of Public Health Science, Shanxi Medical University, Taiyuan 030001, China. sxlqs2012@163.com.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C000607131:2,4',5'-trihydroxyl-5,2'-dibromodiphenylmethanone; D001577:Benzophenones; D010636:Phenols; D020011:Protective Agents; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D053148:Caspase 3
keywords: 2,4′,5′-trihydroxyl-5,2′-dibromo diphenylmethanone; EA.hy926 cells; H2O2; apoptosis; microarray analysis