TY - JOUR
T1 - 8,9-Epoxyeicosatrienoic acid analog protects pulmonary artery smooth muscle cells from apoptosis via ROCK pathway
AU - Ma, Jun
AU - Zhang, Lei
AU - Li, Shanshan
AU - Liu, Shulin
AU - Ma, Cui
AU - Li, Weiyang
AU - Falck, J. R.
AU - Manthati, Vijay L.
AU - Reddy, D. Sudarshan
AU - Medhora, Meetha
AU - Jacobs, Elizabeth R.
AU - Zhu, Daling
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China (No. 30470752 ), NIH GM31278 and the Robert A. Welch Foundation (J. Falck), NIH HL069996 (M. Medhora), HL49294 (ER Jacobs).
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - 8,9-EET
KW - 8,9-EET analog
KW - Apoptosis
KW - PASMCs
KW - Rho-kinase
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U2 - 10.1016/j.yexcr.2010.05.013
DO - 10.1016/j.yexcr.2010.05.013
M3 - Article
C2 - 20493836
AN - SCOPUS:77954386544
SN - 0014-4827
VL - 316
SP - 2340
EP - 2353
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 14
ER -