Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: role of reactive oxygen species.
Studies have shown that oxidized low density lipoprotein (ox-LDL) elicits both necrotic and apoptotic cell death and several mechanisms have been proposed. Ox-LDL induces reactive oxygen species (ROS), a second messenger that might be involved in apoptosis, formation in different types of cells including endothelial cells (ECs) and smooth muscle cells (SMCs). As lectin-like ox-LDL receptor-1 (LOX-1) was the main receptor for ox-LDL, this study was designed to determine whether the apoptosis induced by ox-LDL was mediated by LOX-1 in cultured human umbilical vein endothelial cells (HUVECs) and whether there is an association between LOX-1 mediated apoptosis and the production of ROS. After exposure to ox-LDL (50,100, and 150 microg/ml for 18 h), HUVECs exhibit typical apoptotic characteristics as determined by transmission electron microscopy and flow cytometry analysis in a dose-dependent pattern. Ox-LDL increases intracellular ROS formation including superoxide anion (O2-) and hydrogen peroxide (H2O2) in a dose-dependent and time-dependent manner. Pretreatment with anti-LOX-1 mAb, Vitamin C, apocynin or catalase significantly reduced ROS production and prevented ox-LDL-induced apoptosis, while indomethacin or allopurinol had no effect. These results suggest that LOX-1 mediates ox-LDL-induced apoptosis in endothelial cells and that ROS production and NADPH oxidase might play an important role in ox-LDL-induced apoptosis.
Chen
Xiu-ping
XP
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Xun
Ke-li
KL
Wu
Qin
Q
Zhang
Tian-tai
TT
Shi
Jing-shan
JS
Du
Guan-hua
GH
D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000633:toxicity*; D019255:NADPH Oxidases / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051131:Receptors, Oxidized LDL / Q000502:physiology*; D051127:Scavenger Receptors, Class E / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D013481:Superoxides; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D001205:Ascorbic Acid