title: Protective role of autophagy in AGE-induced early injury of human vascular endothelial cells.
abstract: Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetes mellitus and atherosclerosis by promoting vascular endothelial cell proliferation, migration, damage and death. In this study, we examined the role of autophagy in HUVECs exposed to AGE-modified bovine serum albumin (AGE-BSA). HUVECs incubated with AGE-BSA for 6 h showed an increase in the formation of acidic vesicular organelles and autophagosomes. AGE-BSA-induced upregulation of microtubule associated protein 1 light chain 3-II (LC3-II), a marker of autophagy, was abolished by pretreatment with the autophagy inhibitor 3-methyladenine (3-MA), and was increased by rapamycin, an autophagy inducer. The increase of lactate dehydrogenase (LDH) leakage induced by AGE-BSA was increased by 3-MA, but not rapamycin. An oxidative inhibitor, α-tocopherol, decreased not only the AGE-BSA-induced increase of reactive oxygen species, but also the upregulation of LC3-II protein levels. These results suggest that AGE-BSA increases the level of autophagy, which is protective against HUVEC injury, and that ROS play a role in this activation of autophagy.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, Institute of Neuroscience, Soochow University, Suzhou 215004, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: Shou-Jiang
authors.initials: SJ
authors.lastname: You
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Zhang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Han
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Cao
authors.forename: Xing-Shun
authors.initials: XS
authors.lastname: Xu
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D003470:Culture Media / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000633:toxicity*; D020123:Sirolimus / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D003470:Culture Media; D017127:Glycation End Products, Advanced; D020011:Protective Agents; D017382:Reactive Oxygen Species; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; C025946:3-methyladenine; D007770:L-Lactate Dehydrogenase; D024502:alpha-Tocopherol; D000225:Adenine; D020123:Sirolimus