@article{APS5663,
author = {Tao Wang and Zhen-xiang Zhang and Yong-jian Xu and Qing-hua Hu},
title = {5-Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery smooth muscle cells by blocking mitochondrial KATP channels},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {10},
year = {2016},
keywords = {},
abstract = {Aim: To study the effect of 5-hydroxydecanoate (5-HD) on the proliferation of 24 h hypoxic human pulmonary artery smooth muscle cells (HPASMC) and to explore the pharmacological mechanisms of 5-HD as an inhibitor of mitochondrial membrane ATP-sensitive potassium channel activation.
Methods: Normoxic or hy-poxic HPASMC in culture were stimulated by either diazoxide or 5-HD for 24 h. The proliferation of HPASMC was examined by 3- (4,5-dimethyl-2-thiazol-yl) -2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay and proliferating cell nuclear antigen (PCNA) immunohistochemistry staining. The apoptosis of HPASMC was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometric analysis. The relative changes in mitochondrial membrane potential (DeltaPsim) were measured using the rhodamine fluorescence (R-123) technique.
Results: Both hypoxia and diazoxide stimulation increased DeltaPsim value measured by the absorbance of MTT, PCNA-positive staining and decreased TUNEL-positive staining and apoptotic cells in HPASMC. Hypoxia and the concomitant stimulation of diazoxide obviously enhanced the effects of hypoxia or diazoxide alone. 5-HD significantly attenuated the effects in each of the above conditions. Additionally, 5-HD partially inhibited the effect of hypoxia on R-123 fluorescence intensity in HPASMC.
Conclusion: 5-HD can inhibit the proliferation of hypoxic HPASMC by blocking mitochondrial KATP channels.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/5663}
}