title: Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways.
abstract: Advanced Glycation End Products (AGEs) has been implicated in the progression of diabetic keratopathy. However, details regarding their function are not well understood. In the present study, we investigated the effects of intracellular reactive oxygen species (ROS) and JNK, p38 MAPK on AGE-modified bovine serum albumin (BSA) induced Human telomerase-immortalized corneal epithelial cells (HUCLs) apoptosis. We found that AGE-BSA induced HUCLs apoptosis and increased Bax protein expression, decreased Bcl-2 protein expression. AGE-BSA also induced the expression of receptor for advanced glycation end product (RAGE). AGE-BSA-RAGE interaction induced intracellular ROS generation through activated NADPH oxidase and increased the phosphorylation of p47phox. AGE-BSA induced HUCLs apoptosis was inhibited by pretreatment with NADPH oxidase inhibitors, ROS quencher N-acetylcysteine (NAC) or neutralizing anti-RAGE antibodies. We also found that AGE-BSA induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor effectively blocked AGE-BSA-induced HUCLs apoptosis. In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by AGE-BSA. Our results indicate that AGE-BSA induced HUCLs apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways.
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Long
authors.initials: L
authors.lastname: Shi
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yu
authors.forename: Hongling
authors.initials: H
authors.lastname: Yang
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D003316:Corneal Diseases / Q000209:etiology*; D048909:Diabetes Complications / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D019573:Epithelium, Corneal / Q000166:cytology; D016650:Fluorescein-5-isothiocyanate; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D012710:Serum Albumin, Bovine; D048051:p38 Mitogen-Activated Protein Kinases; D019098:Telomerase; D016650:Fluorescein-5-isothiocyanate