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  • 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.

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.

Journal of pharmacological sciences (2012-09-29)
Chie Aoki, Kunihiro Suzuki, Kazunori Yanagi, Hiroko Satoh, Mai Niitani, Yoshimasa Aso
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
1-Deoxynojirimycin hydrochloride
Sigma-Aldrich
Miglitol