5-Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery smooth muscle cells by blocking mitochondrial K(ATP) channels.
OBJECTIVE
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.


CONCLUSIONS
5-HD can inhibit the proliferation of hypoxic HPASMC by blocking mitochondrial K(ATP) channels.
Wang
Tao
T
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. wt7636@sina.com.cn
Zhang
Zhen-Xiang
ZX
Xu
Yong-Jian
YJ
Hu
Qing-Hua
QH
D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003652:Decanoic Acids / Q000494:pharmacology*; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology
D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018809:Proliferating Cell Nuclear Antigen; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid