15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90.

Abstract

AIMS:

15-Hydroxyeicosatetraenoic acid (15-HETE), generated by hypoxia, is a product of arachidonic acid and mainly catalyzed by 15-lipoxygenase (15-LO) in pulmonary artery. As HSP90 is known to be involved in apoptosis in other tissues and cells, we aim to test whether anti-apoptotic effect of 15-HETE is regulated by the molecular chaperone in pulmonary artery smooth muscle cells.

MAIN METHODS:

To test this hypothesis, we performed cell viability analysis, mitochondrial potential assay, caspase-3 activity measurement, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling with and without HSP90 inhibitor.

KEY FINDINGS:

Our results showed that both exogenous and endogenous 15-HETE up-regulated HSP90 expression and prevented PASMC from serum deprivation-induced apoptosis. Serum deprivation lead to mitochondrial membrane depolarization, decreased expression of Bcl-2 and enhanced expression of Bax, and activation of caspase-3 and caspase-9 in PASMCs. 15-HETE reversed all these effects in a HSP90-dependent manner.

SIGNIFICANCE:

This study establishes the factor involved in 15-HETE-protecting PASMC from apoptosis and the regulation of HSP90 by 15-HETE may be an important mechanism underlying the treatment of pulmonary artery hypertension and provide a novel therapeutic target in future.

• Authors: Lei Zhang, Jun Ma, Yaqian Li, Lei Guo, Yajuan Ran, Shulin Liu, Chun Jiang, Daling Zhu
• Journal: Life sciences (Life Sci) Vol. 87 Issue 7-8 Pg. 223-31 (Aug 14 2010) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 20619278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• HSP90 Heat-Shock Proteins
• Hydroxyeicosatetraenoic Acids
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid
• Caspases

Topics

• Animals
• Apoptosis
• Caspases (genetics, metabolism)
• Cell Hypoxia
• Cells, Cultured
• DNA Fragmentation
• Gene Expression Regulation
• HSP90 Heat-Shock Proteins (genetics, metabolism)
• Hydroxyeicosatetraenoic Acids (metabolism)
• Male
• Mitochondria (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Pulmonary Artery (cytology)
• Rats
• Rats, Wistar
• bcl-2-Associated X Protein (genetics, metabolism)