A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor
Plant phytoprostanes (PhytoPs) are lipid oxidative stress mediators that share structural similarities with mammal prostaglandins (PGs). They have been demonstrated to modulate inflammatory processes mediated by prostaglandins. The present study aims to test the effects of the most abundant oxylipin...
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2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2730 |
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| author | Silvia Montoro-García Sara Martínez-Sánchez Miguel Carmena-Bargueño Horacio Pérez-Sánchez María Campillo Camille Oger Jean-Marie Galano Thierry Durand Ángel Gil-Izquierdo José Antonio Gabaldón |
| author_facet | Silvia Montoro-García Sara Martínez-Sánchez Miguel Carmena-Bargueño Horacio Pérez-Sánchez María Campillo Camille Oger Jean-Marie Galano Thierry Durand Ángel Gil-Izquierdo José Antonio Gabaldón |
| author_sort | Silvia Montoro-García |
| collection | DOAJ |
| description | Plant phytoprostanes (PhytoPs) are lipid oxidative stress mediators that share structural similarities with mammal prostaglandins (PGs). They have been demonstrated to modulate inflammatory processes mediated by prostaglandins. The present study aims to test the effects of the most abundant oxylipin from <i>Gracilaria longissima</i>, ent-9-D1t-Phytoprostane (9-D1t-PhytoP), on platelet activation and vascular cells as well as clarify possible interactions with platelets and the endothelial EP3 receptor Platelet and monocyte activation was assessed by flow cytometry in the presence of purified 9-D1t-PhytoP. Cell migration was studied using the human Ea.hy926 cell line by performing a scratch wound healing assay. The RNA expression of inflammatory markers was evaluated by RT-PCR under inflammatory conditions. Blind docking consensus was applied to the study of the interactions of selected ligands against the EP3 receptor protein. The 9D1t-PhytoP exerts several pharmacological effects; these include prothrombotic and wound-healing properties. In endothelial cells, 9D1t-PhytP mimics the migration stimulus of PGE<sub>2</sub>. Computational analysis revealed that 9D1t-PhytP forms a stable complex with the hydrophobic pocket of the EP3 receptor by interaction with the same residues as misoprostol and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), thus supporting its potential as an EP3 agonist. The potential to form procoagulant platelets and the higher endothelial migration rate of the 9-D1t-PhytoP, together with its capability to interact with PGE<sub>2</sub> main target receptor in platelets suggest herein that this oxylipin could be a strong candidate for pharmaceutical research from a multitarget perspective. |
| first_indexed | 2024-03-11T09:40:38Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:40:38Z |
| publishDate | 2023-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2cdac46416df458692f3111dbea4465d2023-11-16T17:01:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243273010.3390/ijms24032730A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin ReceptorSilvia Montoro-García0Sara Martínez-Sánchez1Miguel Carmena-Bargueño2Horacio Pérez-Sánchez3María Campillo4Camille Oger5Jean-Marie Galano6Thierry Durand7Ángel Gil-Izquierdo8José Antonio Gabaldón9Izpisua Lab, HiTech, Health Sciences Department, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos 135, 30107 Guadalupe, SpainIzpisua Lab, HiTech, Health Sciences Department, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos 135, 30107 Guadalupe, SpainStructural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos 135, 30107 Guadalupe, SpainStructural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos 135, 30107 Guadalupe, SpainIzpisua Lab, HiTech, Health Sciences Department, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos 135, 30107 Guadalupe, SpainInstitut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS, Faculty of Pharmacy, University of Montpellier-ENSCM, 34093 Montpellier, FranceInstitut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS, Faculty of Pharmacy, University of Montpellier-ENSCM, 34093 Montpellier, FranceInstitut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS, Faculty of Pharmacy, University of Montpellier-ENSCM, 34093 Montpellier, FranceResearch Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, University Campus of Espinardo, Edif. 25, 30100 Espinardo, SpainMolecular Recognition and Encapsulation Research Group (REM), Health Sciences Department, Universidad Católica de Murcia (UCAM), Campus de los Jerónimos 135, 30107 Guadalupe, SpainPlant phytoprostanes (PhytoPs) are lipid oxidative stress mediators that share structural similarities with mammal prostaglandins (PGs). They have been demonstrated to modulate inflammatory processes mediated by prostaglandins. The present study aims to test the effects of the most abundant oxylipin from <i>Gracilaria longissima</i>, ent-9-D1t-Phytoprostane (9-D1t-PhytoP), on platelet activation and vascular cells as well as clarify possible interactions with platelets and the endothelial EP3 receptor Platelet and monocyte activation was assessed by flow cytometry in the presence of purified 9-D1t-PhytoP. Cell migration was studied using the human Ea.hy926 cell line by performing a scratch wound healing assay. The RNA expression of inflammatory markers was evaluated by RT-PCR under inflammatory conditions. Blind docking consensus was applied to the study of the interactions of selected ligands against the EP3 receptor protein. The 9D1t-PhytoP exerts several pharmacological effects; these include prothrombotic and wound-healing properties. In endothelial cells, 9D1t-PhytP mimics the migration stimulus of PGE<sub>2</sub>. Computational analysis revealed that 9D1t-PhytP forms a stable complex with the hydrophobic pocket of the EP3 receptor by interaction with the same residues as misoprostol and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), thus supporting its potential as an EP3 agonist. The potential to form procoagulant platelets and the higher endothelial migration rate of the 9-D1t-PhytoP, together with its capability to interact with PGE<sub>2</sub> main target receptor in platelets suggest herein that this oxylipin could be a strong candidate for pharmaceutical research from a multitarget perspective.https://www.mdpi.com/1422-0067/24/3/2730phytoprostanesprostaglandinsplateletsEP3 receptormigrationinflammation |
| spellingShingle | Silvia Montoro-García Sara Martínez-Sánchez Miguel Carmena-Bargueño Horacio Pérez-Sánchez María Campillo Camille Oger Jean-Marie Galano Thierry Durand Ángel Gil-Izquierdo José Antonio Gabaldón A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor International Journal of Molecular Sciences phytoprostanes prostaglandins platelets EP3 receptor migration inflammation |
| title | A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor |
| title_full | A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor |
| title_fullStr | A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor |
| title_full_unstemmed | A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor |
| title_short | A Phytoprostane from <i>Gracilaria longissima</i> Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor |
| title_sort | phytoprostane from i gracilaria longissima i increases platelet activation platelet adhesion to leukocytes and endothelial cell migration by potential binding to ep3 prostaglandin receptor |
| topic | phytoprostanes prostaglandins platelets EP3 receptor migration inflammation |
| url | https://www.mdpi.com/1422-0067/24/3/2730 |
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