The role of ERK1/2 in 15-HETE-inhibited apoptosis in pulmonary arterial smooth muscle cells
| Autor: | Jun Ma, Zhigang Wang, Jing Jiang, Shuang Wang, Shu-Lin Liu, Weiyang Li, Daling Zhu |
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| Rok vydání: | 2010 |
| Předmět: |
Male
MAPK/ERK pathway Cell Survival MAP Kinase Signaling System Myocytes Smooth Muscle Apoptosis X-Linked Inhibitor of Apoptosis Protein Pulmonary Artery Biology Inhibitor of apoptosis Biochemistry Hydroxyeicosatetraenoic Acids In Situ Nick-End Labeling medicine Animals Myocyte Viability assay Rats Wistar Protein Kinase Inhibitors Molecular Biology Membrane Potential Mitochondrial Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 TUNEL assay Kinase PTEN Phosphohydrolase Cell Biology medicine.disease Molecular biology Pulmonary hypertension Rats Enzyme Activation Proto-Oncogene Proteins c-bcl-2 |
| Zdroj: | Journal of Receptors and Signal Transduction. 31:45-52 |
| ISSN: | 1532-4281 1079-9893 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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