Document Detail

Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells.
MedLine Citation:
PMID:  22493087     Owner:  NLM     Status:  MEDLINE    
Pulmonary artery endothelial plexiform lesion is responsible for pulmonary vascular remodeling (PVR), a basic pathological change of pulmonary arterial hypertension (PAH). Recent evidence suggests that epoxyeicosatrienoic acid (EET), which is derived from arachidonic acid by cytochrome p450 (CYP) epoxygenase, has an essential role in PAH. However, until now, most research has focused on pulmonary vasoconstriction; it is unclear whether EET produces mitogenic and angiogenic effects in pulmonary artery endothelial cells (PAEC). Here we found that 500 nM/l 8,9-EET, 11,12-EET, and 14,15-EET markedly augmented JNK and c-Jun activation in PAECs and that the activation of c-Jun was mediated by JNK, but not the ERK or p38 MPAK pathway. Moreover, treatment with 8,9-EET, 11,12-EET, and 14,15-EET promoted cell proliferation and cell-cycle transition from the G0/G1 phase to S phase and stimulated tube formation in vitro. All these effects were reversed after blocking JNK with Sp600125 (a JNK inhibitor) or JNK1/2 siRNA. In addition, the apoptotic process was alleviated by three EET region isomers through the JNK/c-Jun pathway. These observations suggest that 8,9-EET, 11,12-EET, and 14,15-EET stimulate PAEC proliferation and angiogenesis, as well as protect the cells from apoptosis, via the JNK/c-Jun pathway, an important underlying mechanism that may promote PAEC growth and angiogenesis during PAH.
Jun Ma; Lei Zhang; Weina Han; Tingting Shen; Cui Ma; Yun Liu; Xiaowei Nie; Mengmeng Liu; Yajuan Ran; Daling Zhu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-05
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-10     Completed Date:  2012-09-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1093-105     Citation Subset:  IM    
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University Daqing, Daqing 163319, China.
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MeSH Terms
8,11,14-Eicosatrienoic Acid / pharmacology*
Active Transport, Cell Nucleus / drug effects
Apoptosis / drug effects
Cell Nucleus / drug effects,  metabolism
Cell Proliferation / drug effects
Cell Survival / drug effects
Endothelial Cells / cytology,  drug effects*,  enzymology,  metabolism*
Enzyme Activation / drug effects
Gene Silencing
Interphase / drug effects
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors,  deficiency,  genetics,  metabolism*
Muscle, Smooth, Vascular / cytology
Neovascularization, Physiologic / drug effects*
Phosphoproteins / metabolism
Protein Kinase Inhibitors / pharmacology
Pulmonary Artery / cytology*
Signal Transduction / drug effects
Vasodilator Agents / pharmacology*
Reg. No./Substance:
0/Phosphoproteins; 0/Protein Kinase Inhibitors; 0/Vasodilator Agents; 7324-41-6/8,11,14-Eicosatrienoic Acid; EC Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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