15-HETE suppresses K(+) channel activity and inhibits apoptosis in pulmonary artery smooth muscle cells.
15-Hydroxyeicosatetraenoic acid (15-HETE) is an important hypoxic product from arachidonic acid (AA) in the wall of pulmonary vessels. Although its effects on pulmonary artery constriction are well known, it remains unclear whether 15-HETE acts on the apoptotic responses in pulmonary artery smooth muscle cells (PASMCs) and whether K(+) channels participate in this process. These hypothesises were validated by cell viability assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, mitochondrial potentials assay, caspase activity assay and western blot. We found that 15-HETE enhanced cell survival, suppressed the expression and activity of caspase-3, upregulated bcl-2 and attenuated mitochondrial depolarization, prevented chromatin condensation and partly reversed K(+) channel opener-induced apoptosis in PASMCs under serum-deprived conditions. Our data indicated that 15-HETE inhibits the apoptosis in PASMCs through, at least in part, inactivating K(+) channels.
Li
Yumei
Y
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150081, Heilongjiang, People's Republic of China.
Li
Qian
Q
Wang
Zhigang
Z
Liang
Di
D
Liang
Shujun
S
Tang
Xiaobo
X
Guo
Lei
L
Zhang
Rong
R
Zhu
Daling
D
D017209:Apoptosis; D016718:Arachidonic Acid / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D000860:Hypoxia; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011651:Pulmonary Artery / Q000473:pathology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D015221:Potassium Channels; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D013844:Thiazoles; D016718:Arachidonic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D006861:Hydrogen Peroxide; D053148:Caspase 3; C022616:thiazolyl blue; D011188:Potassium