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.
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The study was supported by grants from the National Natural Chinese Science Foundation (No 30370623).
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Wang, T., Zhang, Zx., Xu, Yj. et al. 5-Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery smooth muscle cells by blocking mitochondrial KATP channels. Acta Pharmacol Sin 28, 1531–1540 (2007). https://doi.org/10.1111/j.1745-7254.2007.00636.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00636.x
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