5-Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery smooth muscle cells by blocking mitochondrial K(ATP) channels |
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Authors: | Wang Tao Zhang Zhen-Xiang Xu Yong-Jian Hu Qing-Hua |
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Affiliation: | Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. wt7636@sina.com.cn |
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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 hypoxic 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 (deltaPhi(m)) were measured using the rhodamine fluorescence (R-123) technique. RESULTS: Both hypoxia and diazoxide stimulation increased deltaPhi(m) 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 K(ATP) channels. |
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Keywords: | pulmonary artery smooth muscle cell hypoxia 5-hydroxydecanoate mitochond-rial membrane ATP-sensitive potassiumchannel |
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