title: The role of ERK1/2 in 15-HETE-inhibited apoptosis in pulmonary arterial smooth muscle cells.
abstract: 15-Hydroxyeicosatetrenoic acid (15-HETE) is an important product of arachidonic acid catalyzed by 15-lipoxygenase (15-LO) in the wall of pulmonary vessels, which plays a key role in pulmonary arterial hypertension. The previous studies showed that 15-HETE inhibits apoptosis. It is still unknown, however, whether 15-HETE acts on the apoptotic responses through the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. The aim of the study is to test the hypothesis that ERK1/2 pathway participates in the protective effects of 15-HETE on the cell survival. This hypothesis was validated by cell viability measurement, nuclear morphology determination, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, mitochondrial potentials assay and Western blot. We found that 15-HETE enhanced cell survival, suppressed the expression of phosphatase and tensin homologue deleted on chromosome ten, upregulated X-linked inhibitor of apoptosis protein and Bcl-2 and attenuated mitochondrial depolarization in pulmonary artery muscle smooth cells (PASMCs) under serum-deprived conditions. These effects were reversed by ERK1/2 inhibitor PD98059. Taken together, our data indicated that the ERK1/2 kinase is a regulator of PASMC apoptosis, and potential therapeutical strategy for pulmonary hypertension may be developed by targeting at intracellular signaling systems centered by the kinase.
authors.affiliation: Institute of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Shulin
authors.initials: S
authors.lastname: Liu
authors.forename: Weiyang
authors.initials: W
authors.lastname: Li
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051059:PTEN Phosphohydrolase