血管内皮細胞株 bEnd.3 細胞におけるアペリンによる終末糖化産物誘発細胞死抑制作用

• Published in: 日本薬理学会年会要旨集 p. 1-P2-09
• Main Authors: 石丸, 侑希, 山本, 時駆, 吉澤, 成宣, 吉岡, 靖啓, 山室, 晶子, 前田, 定秋
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: cell death; cytoprotection; endothelial cell
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_1-P2-09

Endothelial dysfunction, including cell death of endothelial cells, has been known to be one of the key factors in the pathogenesis of diabetes-related complications. It has been reported that advanced glycation end products (AGEs) contribute the damage of endothelial cells in diabetes. In this study, we investigated the effect of apelin on AGEs-induced cell death in mouse endothelial cell line bEnd.3. AGEs of bovine serum albumin (AGE-BSA) was prepared by incubating BSA and D-glyceraldehyde under sterile conditions at 37°C for 7 days and followed by purification using an ultrafiltration spin column. Cell death was evaluated by Hoechst 33342/propidium iodide double-staining. Treatment of bEnd.3 cells with AGE-BSA (1 mg/mL) induced cell death in a time-dependent manner. The AGE-BSA-induced cell death was attenuated in the presence of [Pyr1]-apelin-13 (10 μM). ML211, an antagonist of apelin receptor APJ, inhibited the cytoprotective effect of apelin. The cytoprotective effect of apelin was also prevented by LY294002, a PI3K inhibitor, but not by PD98059 and SP600125, inhibitors of MEK1 and JNK, respectively. These results suggest that apelin protects bEnd.3 cells from AGEs-induced cell death by activating PI3K signaling pathway via stimulation of APJ and that apelin may attenuate the damage of endothelial cells in diabetes.