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: Jing Jiang, Shuang Wang, Zhigang Wang, Jun Ma, Shulin Liu, Weiyang Li, Daling Zhu
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 31 Issue 1 Pg. 45-52 (Feb 2011) ISSN: 1532-4281 [Electronic] England
• PMID: 20822476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxyeicosatetraenoic Acids
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• X-Linked Inhibitor of Apoptosis Protein
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• PTEN Phosphohydrolase

Topics

• Animals
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Enzyme Activation (drug effects)
• Hydroxyeicosatetraenoic Acids (pharmacology)
• In Situ Nick-End Labeling
• MAP Kinase Signaling System (drug effects)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
• Myocytes, Smooth Muscle (cytology, drug effects, enzymology)
• PTEN Phosphohydrolase (metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Pulmonary Artery (cytology)
• Rats
• Rats, Wistar
• X-Linked Inhibitor of Apoptosis Protein (metabolism)