title: EGb 761 Protects Cardiac Microvascular Endothelial Cells against Hypoxia/Reoxygenation Injury and Exerts Inhibitory Effect on the ATM Pathway.
abstract: Ginkgo biloba extract (EGb 761) has been widely used clinically to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.
authors.affiliation: Department of Cardiovascular Surgery, Nanyang Affiliated Hospital of Zhengzhou University, Nanyang Central Hospital, Nanyang, Henan Province 473009, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, Nanyang Affiliated Hospital of Zhengzhou University, Nanyang Central Hospital, Nanyang, Henan Province 473009, P.R. China.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Nanyang Affiliated Hospital of Zhengzhou University, Nanyang Central Hospital, Nanyang, Henan Province 473009, P.R. China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, Nanyang Affiliated Hospital of Zhengzhou University, Nanyang Central Hospital, Nanyang, Henan Province 473009, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Cardiovascular Surgery, Nanyang Affiliated Hospital of Zhengzhou University, Nanyang Central Hospital, Nanyang, Henan Province 473009, P.R. China.
authors.forename: Kan
authors.initials: K
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D020441:Ginkgo biloba / Q000737:chemistry*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D064007:Ataxia Telangiectasia Mutated Proteins; D053148:Caspase 3
keywords: EGb 761; ataxia-telangiectasia mutated (ATM); hypoxia/reoxygenation (H/R) injury; microvascular endothelial cells; myocardial ischemia reperfusion injury