PMID- 17883937
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20070921
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 28
IP  - 10
DP  - 2007 Oct
TI  - 5-Hydroxydecanoate inhibits proliferation of hypoxic human pulmonary artery 
      smooth muscle cells by blocking mitochondrial K(ATP) channels.
PG  - 1531-40
AB  - 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.
FAU - Wang, Tao
AU  - Wang T
AD  - Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430030, China. 
      wt7636@sina.com.cn
FAU - Zhang, Zhen-Xiang
AU  - Zhang ZX
FAU - Xu, Yong-Jian
AU  - Xu YJ
FAU - Hu, Qing-Hua
AU  - Hu QH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Decanoic Acids)
RN  - 0 (Hydroxy Acids)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (mitochondrial K(ATP) channel)
RN  - 624-00-0 (5-hydroxydecanoic acid)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Hypoxia
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Decanoic Acids/*pharmacology
MH  - Humans
MH  - Hydroxy Acids/*pharmacology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Muscle, Smooth, Vascular/cytology/drug effects/metabolism
MH  - Myocytes, Smooth Muscle/cytology/*drug effects/metabolism
MH  - Potassium Channel Blockers/pharmacology
MH  - Potassium Channels/metabolism/*physiology
MH  - Proliferating Cell Nuclear Antigen/metabolism
MH  - Pulmonary Artery/cytology
EDAT- 2007/09/22 09:00
MHDA- 2008/11/19 09:00
CRDT- 2007/09/22 09:00
PHST- 2007/09/22 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2007/09/22 09:00 [entrez]
AID - 10.1111/j.1745-7254.2007.00636.x [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2007 Oct;28(10):1531-40. doi: 
      10.1111/j.1745-7254.2007.00636.x.