Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S]
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) ep...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-06-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520317028 |
| _version_ | 1819077236633894912 |
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| author | Jun Ma Lei Zhang Weina Han Tingting Shen Cui Ma Yun Liu Xiaowei Nie Mengmeng Liu Yajuan Ran Daling Zhu |
| author_facet | Jun Ma Lei Zhang Weina Han Tingting Shen Cui Ma Yun Liu Xiaowei Nie Mengmeng Liu Yajuan Ran Daling Zhu |
| author_sort | Jun Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:54:00Z |
| format | Article |
| id | doaj.art-7037a4109a6942ba862084b2fe5eeac9 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T18:54:00Z |
| publishDate | 2012-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7037a4109a6942ba862084b2fe5eeac92022-12-21T18:53:40ZengElsevierJournal of Lipid Research0022-22752012-06-0153610931105Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S]Jun Ma0Lei Zhang1Weina Han2Tingting Shen3Cui Ma4Yun Liu5Xiaowei Nie6Mengmeng Liu7Yajuan Ran8Daling Zhu9Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, ChinaDepartment of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;To whom correspondence should be addressed.; Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing 163319, China;; Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081, China; To whom correspondence should be addressed.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.http://www.sciencedirect.com/science/article/pii/S0022227520317028epoxyeicosatrienoic acidcell cycleapoptosisc-Jun N-terminal kinase |
| spellingShingle | Jun Ma Lei Zhang Weina Han Tingting Shen Cui Ma Yun Liu Xiaowei Nie Mengmeng Liu Yajuan Ran Daling Zhu Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S] Journal of Lipid Research epoxyeicosatrienoic acid cell cycle apoptosis c-Jun N-terminal kinase |
| title | Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S] |
| title_full | Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S] |
| title_fullStr | Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S] |
| title_full_unstemmed | Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S] |
| title_short | Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells[S] |
| title_sort | activation of jnk c jun is required for the proliferation survival and angiogenesis induced by eet in pulmonary artery endothelial cells s |
| topic | epoxyeicosatrienoic acid cell cycle apoptosis c-Jun N-terminal kinase |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520317028 |
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