Open Access5‐Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery smooth muscle cells by blocking mitochondrial K ATP channels 1
Author(s) -
WANG Tao,
ZHANG Zhenxiang,
XU Yongjian,
HU Qinghua
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00636.x
Subject(s) - tunel assay , diazoxide , mtt assay , microbiology and biotechnology , apoptosis , biology , hypoxia (environmental) , rhodamine 123 , pharmacology , chemistry , biochemistry , endocrinology , oxygen , organic chemistry , multiple drug resistance , insulin , antibiotics
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‐ 2 H ‐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 (ΔΨ m ) were measured using the rhodamine fluorescence (R‐123) technique. Results: Both hypoxia and diazoxide stimulation increased ΔΨ 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.