title: Miglitol, an anti-diabetic drug, inhibits oxidative stress-induced apoptosis and mitochondrial ROS over-production in endothelial cells by enhancement of AMP-activated protein kinase.
abstract: Endothelial dysfunction caused by oxidative stress plays a key role in atherogenesis. This study investigated whether the anti-diabetic drug miglitol, an α-glucosidase inhibitor, which is currently available in clinical practice, can prevent endothelial cell apoptosis and whether it might restore impaired vascular relaxation under oxidative stress. The bEnd.3 cells, a microvascular endothelial cell line, were pre-treated with various concentrations of miglitol and then were incubated with H(2)O(2) for 1 - 2 h. Treatment of bEnd.3 cells with miglitol resulted in the protection of cell viability, suppression of mitochondrial superoxide production, and DNA strand breakage under the oxidative stress. These effects of miglitol were associated with the activation of AMP-activated protein kinase (AMPK) and the phosphorylation of endothelial nitric oxide synthase (eNOS). In aortic rings with endothelium, acetylcholine (Ach)-induced relaxation was attenuated by H(2)O(2). We found that this impaired relaxation was restored by acute treatment with miglitol. Compound C, an AMPK inhibitor, inhibited the amelioration of vascular relaxations treated with miglitol. These results suggest that miglitol might protect against endothelial cells damage under oxidative stress via inhibition of endothelial cell apoptosis and mitochondrial superoxide production, which are mediated by the activation of AMPK and the phosphorylation of eNOS.
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Aoki
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yanagi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Satoh
authors.forename: Mai
authors.initials: M
authors.lastname: Niitani
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Aso
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002460:Cell Line; D004249:DNA Damage; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D017931:DNA Primers; D007004:Hypoglycemic Agents; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; C045621:miglitol; D018799:Intercellular Adhesion Molecule-1; D017485:1-Deoxynojirimycin; D006861:Hydrogen Peroxide; D000263:Adenylate Kinase