eng URI http://hdl.handle.net/10795/3296 ιατρική βιοχημεία κυτταρολογία Background: Advanced glycation end products (AGEs), the final products of the Maillard reaction, have been shown to impair endothelial proliferation and function, thus contributing to endothelial cell injury present in diabetes, inflammatory and cardiovascular diseases. Endoplasmic reticulum (ER) stress triggered under hyperglycemic, hypoxic and oxidative conditions has been implicated in endothelial dysfunction through activation of the unfolded protein response (UPR). The present study investigates the role of AGEs in ER stress induction in human aortic endothelial cells exposed to variable AGE treatments. Methods: Human aortic endothelial cells (HAEC) were treated with increasing concentrations (100, 200 μg/mL) of AGE-bovine serum albumin (AGE-BSA) at different time-points (24, 48, 72 h). The induction of ER stress and the involved UPR components were investigated on mRNA and protein levels. Apoptosis was quantitatively determined by flow cytometry detecting propidium iodide expression and annexin V binding simultaneously. Results: AGEs administration significantly reduced HAEC proliferation in a time- and dose-dependent manner. An immediate induction of the ER chaperones GRP78, GRP94 and the transcriptional activator, XBP-1 was observed at 24 h and 48 h. A later induction of the phospho-lF2α and proapoptotic transcription factor CHOP was observed at 48 h and 72 h, being correlated with elevated early apoptotic cell numbers at the same time-points. Conclusions: The present study demonstrates that AGEs directly induce ER stress in human aortic endothelial cells, playing an important role in endothelial cell apoptosis. Targeting AGEs signaling pathways in order to alleviate ER stress may prove of therapeutic potential to endothelial dysfunction-related disorders. 10 pp. LOMv1.0 creator LOMv1.0 publisher LOMv1.0 Scientific Coordinator LOMv1.0 Project Executing Organisation 2013-01-07 Digital Library of the Operational Programme "Education and Lifelong Learning" abstract types Text Advanced Glycation End-products Polycystic ovary syndrome Endothelium Endothelial cells Μικροβιολογία Μοριακή βιολογία Γλυκοζυλίωση AGEs PCOS Κύτταρα Σύνδρομο πολυκυστικών ωοθηκών Ενδοθηλίνη 949026 application/pdf http://repository.edulll.gr/edulll/bitstream/10795/3296/2/3296_1.68_%ce%94%ce%97%ce%9c_7_2_13.pdf URI http://hdl.handle.net/10795/3296 LOMv1.0creator 2016-05-20T11:31:32Z LOMv1.0validator 2016-05-20T11:31:32Z LOMv1.0 gre no no Copyright EYD-EPEDBM (Operational Programme "Education and Lifelong Learning")