title: Hypoxanthine causes endothelial dysfunction through oxidative stress-induced apoptosis.
abstract: Endothelial cell injury and dysfunction caused by reactive oxygen species (ROS) are implicated in the pathogenesis of vascular diseases. ROS are generated and hypoxanthine is degraded by xanthine oxidase. Smoking and alcohol consumption are associated with an increased level of hypoxanthine. We aimed to study the direct role of hypoxanthine in endothelial dysfunction in human umbilical vascular endothelial cells (HUVECs). Hypoxanthine induced cell death and production of ROS. Furthermore, hypoxanthine induced apoptosis through regulation of protein expression related to apoptosis. When cells were pretreated with N-acetylcysteine or a pancaspase inhibitor (Z-VAD-fmk) and stimulated with hypoxanthine, Z-VAD-fmk and N-acetylcysteine prevented hypoxanthine-induced apoptosis by inhibiting the ROS production and caspase pathway. Thus, an increased extracellular concentration of hypoxanthine induces endothelial dysfunction through ROS production and regulates expression of apoptosis-related proteins in HUVECs. These effects are expected to be associated with some vascular diseases.
authors.affiliation: Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, South Korea; Cell and Matrix Research Institute, Kyungpook National University, Daegu, South Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea; Cell and Matrix Research Institute, Kyungpook National University, Daegu, South Korea.
authors.forename: Hye-Myung
authors.initials: HM
authors.lastname: Ryu
authors.affiliation: Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea; Cell and Matrix Research Institute, Kyungpook National University, Daegu, South Korea.
authors.forename: Chan-Duck
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea; Cell and Matrix Research Institute, Kyungpook National University, Daegu, South Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, South Korea; Cell and Matrix Research Institute, Kyungpook National University, Daegu, South Korea. Electronic address: ylkim@knu.ac.kr.
authors.forename: Yong-Lim
authors.initials: YL
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D019271:Hypoxanthine
keywords: Apoptosis; Endothelial cell; Hypoxanthine; Reactive oxygen species