8,9-Epoxyeicosatrienoic acid analog protects pulmonary artery smooth muscle cells from apoptosis via ROCK pathway

Jun Ma, Lei Zhang, Shanshan Li, Shulin Liu, Cui Ma, Weiyang Li, J. R. Falck, Vijay L. Manthati, D. Sudarshan Reddy, Meetha Medhora, Elizabeth R. Jacobs, Daling Zhu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2340-2353
Number of pages14
JournalExperimental Cell Research
Volume316
Issue number14
DOIs
StatePublished - Aug 2010

Fingerprint

Pulmonary Artery
Smooth Muscle Myocytes
Apoptosis
Serum
rho-Associated Kinases
Acids
8,9-epoxyeicosatrienoic acid
Caspase 9
In Situ Nick-End Labeling
Mitochondrial Membranes
Cardiovascular System
Starvation
Cardiac Myocytes
Arachidonic Acid
Caspase 3
Cytochrome P-450 Enzyme System
Cell Survival
Endothelial Cells

Keywords

  • 8,9-EET
  • 8,9-EET analog
  • Apoptosis
  • PASMCs
  • Rho-kinase

ASJC Scopus subject areas

  • Cell Biology

Cite this

8,9-Epoxyeicosatrienoic acid analog protects pulmonary artery smooth muscle cells from apoptosis via ROCK pathway. / Ma, Jun; Zhang, Lei; Li, Shanshan; Liu, Shulin; Ma, Cui; Li, Weiyang; Falck, J. R.; Manthati, Vijay L.; Reddy, D. Sudarshan; Medhora, Meetha; Jacobs, Elizabeth R.; Zhu, Daling.

In: Experimental Cell Research, Vol. 316, No. 14, 08.2010, p. 2340-2353.

Research output: Contribution to journalArticle

Ma, J, Zhang, L, Li, S, Liu, S, Ma, C, Li, W, Falck, JR, Manthati, VL, Reddy, DS, Medhora, M, Jacobs, ER & Zhu, D 2010, '8,9-Epoxyeicosatrienoic acid analog protects pulmonary artery smooth muscle cells from apoptosis via ROCK pathway', Experimental Cell Research, vol. 316, no. 14, pp. 2340-2353. https://doi.org/10.1016/j.yexcr.2010.05.013
Ma, Jun ; Zhang, Lei ; Li, Shanshan ; Liu, Shulin ; Ma, Cui ; Li, Weiyang ; Falck, J. R. ; Manthati, Vijay L. ; Reddy, D. Sudarshan ; Medhora, Meetha ; Jacobs, Elizabeth R. ; Zhu, Daling. / 8,9-Epoxyeicosatrienoic acid analog protects pulmonary artery smooth muscle cells from apoptosis via ROCK pathway. In: Experimental Cell Research. 2010 ; Vol. 316, No. 14. pp. 2340-2353.
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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.

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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.

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