8,9-Epoxyeicosatrienoic acid analog protects pulmonary artery smooth muscle cells from apoptosis via ROCK pathway. Exp Cell Res 2010 Aug 15;316(14):2340-53
Date
05/25/2010Pubmed ID
20493836Pubmed Central ID
PMC2927814DOI
10.1016/j.yexcr.2010.05.013Scopus ID
2-s2.0-77954386544 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid (AA) catalyzed by cytochrome P450 (CYP), have many essential biologic roles in the cardiovascular system including inhibition of apoptosis in cardiomyocytes. In the present study, we tested the potential of 8,9-EET and derivatives to protect pulmonary artery smooth muscle cells (PASMCs) from starvation induced apoptosis. We found 8,9-epoxy-eicos-11(Z)-enoic acid (8,9-EET analog (214)), but not 8,9-EET, increased cell viability, decreased activation of caspase-3 and caspase-9, and decreased TUNEL-positive cells or nuclear condensation induced by serum deprivation (SD) in PASMCs. These effects were reversed after blocking the Rho-kinase (ROCK) pathway with Y-27632 or HA-1077. Therefore, 8,9-EET analog (214) protects PASMC from serum deprivation-induced apoptosis, mediated at least in part via the ROCK pathway. Serum deprivation of PASMCs resulted in mitochondrial membrane depolarization, decreased expression of Bcl-2 and enhanced expression of Bax, all effects were reversed by 8,9-EET analog (214) in a ROCK dependent manner. Because 8,9-EET and not the 8,9-EET analog (214) protects pulmonary artery endothelial cells (PAECs), these observations suggest the potential to differentially promote apoptosis or survival with 8,9-EET or analogs in pulmonary arteries.
Author List
Ma J, Zhang L, Li S, Liu S, Ma C, Li W, Falck JR, Manthati VL, Reddy DS, Medhora M, Jacobs ER, Zhu DMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
Apoptosis
Blotting, Western
Cell Survival
Cells, Cultured
Male
Molecular Structure
Myocytes, Smooth Muscle
Pulmonary Artery
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Vasodilator Agents
rho-Associated Kinases
