Τίτλος:
Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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-elF2á 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. © 2014 by Walter de Gruyter Berlin Boston.
Συγγραφείς:
Adamopoulos, C.
Farmaki, E.
Spilioti, E.
Kiaris, H.
Piperi, C.
Papavassiliou, A.G.
Περιοδικό:
Clinical Chemistry and Laboratory Medicine (CCLM)
Λέξεις-κλειδιά:
advanced glycation end product; bovine serum albumin; chaperone; glucose regulated protein 78; glucose regulated protein 94; growth arrest and DNA damage inducible protein 153; lipocortin 5; messenger RNA; propidium iodide; X box binding protein 1, apoptosis; article; cattle; cell count; cell proliferation; controlled study; endoplasmic reticulum stress; endothelium cell; flow cytometry; human; human aortic endothelial cell; human cell; nonhuman; priority journal; protein expression, Animals; Aorta; Apoptosis; Cattle; Cell Line; Cell Proliferation; DNA-Binding Proteins; Endoplasmic Reticulum Stress; Endothelial Cells; Glycosylation End Products, Advanced; Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Membrane Proteins; RNA, Messenger; Serum Albumin, Bovine; Transcription Factor CHOP; Transcription Factors; Unfolded Protein Response
DOI:
10.1515/cclm-2012-0826
