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5-Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery smooth muscle cells by blocking mitochondrial KATP channels

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Abstract:

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 (ΔΨm) were measured using the rhodamine fluorescence (R-123) technique. Results: Both hypoxia and diazoxide stimulation increased ΔΨm 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.

Keywords: 5-hydroxydecanoate; hypoxia; mitochond-rial membrane ATP-sensitive potassium channel; pulmonary artery smooth muscle cell

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2007.00636.x

Affiliations: 1: Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2: Key Laboratory of Pulmonary Diseases of the Ministry of Health of China and Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Publication date: October 1, 2007

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