title: Curcumin attenuates endothelial cell oxidative stress injury through Notch signaling inhibition.
abstract: Previous studies have demonstrated that Notch signaling pathway plays a regulatory role in cellular oxidative stress injury (OSI). In this study, our aim was to explore the role of the Notch signaling pathway in hydrogen peroxide (H(2)O(2))-induced OSI and the protective effect of curcumin during (H(2)O(2))-induced injury in human umbilical vein endothelial cells (HUVECs). DAPT, a specific inhibitor of the Notch signaling pathway, and Notch1 siRNA were used to study Notch activity. Further, HUVECs were exposed to H(2)O(2) in the absence or presence of curcumin. DAPT and Notch1 siRNA significantly inhibited OSI and the expression of Notch1 and Hes1. Curcumin conferred a protective effect on the HUVECs against H(2)O(2), which was evidenced by improved cell viability, adhesive ability and migratory ability and a decreased apoptotic index, decreased production of reactive oxygen species (ROS) and a reduction in several biochemical parameters. Immunofluorescence and Western blotting analyses demonstrated that H(2)O(2) treatment upregulated the expression of Notch1, Hes1, Caspase3, Bax and cytochrome c downregulated the expression of Bcl2, and treatment with curcumin reversed these effects. We demonstrated for the first time that the inhibition of Notch signaling pathway imparts a protective effect against endothelial OSI. The protective effects of curcumin against OSI are at least in part dependent on Notch1 inhibition.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Weixun
authors.initials: W
authors.lastname: Duan
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Liang
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Yan
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Yu
authors.forename: Zhenxiao
authors.initials: Z
authors.lastname: Jin
authors.forename: Dinghua
authors.initials: D
authors.lastname: Yi
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000072056:Transcription Factor HES-1; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D003474:Curcumin; D045304:Cytochromes c; D004151:Dipeptides; D018398:Homeodomain Proteins; D006861:Hydrogen Peroxide; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; D051028:bcl-2-Associated X Protein; C489735:Hes1 protein, rat; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester