A Phytoprostane from Gracilaria longissima Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor

被引：1

作者：

Montoro-Garcia, Silvia ^{[1
]}

Martinez-Sanchez, Sara ^{[1
]}

Carmena-Bargueno, Miguel ^{[2
]}

Perez-Sanchez, Horacio ^{[2
]}

Campillo, Maria ^{[1
]}

Oger, Camille ^{[3
]}

Galano, Jean-Marie ^{[3
]}

Durand, Thierry ^{[3
]}

Gil-Izquierdo, Angel ^{[4
]}

Antonio Gabaldon, Jose ^{[5
]}

机构：

[1] Univ Catolica Murcia UCAM, Hlth Sci Dept, Izpisua Lab, HiTech, Campus Jeronimos 135, Guadalupe 30107, Spain

[2] Univ Catolica Murcia UCAM, Comp Engn Dept, Struct Bioinformat & High Performance Comp Res Gr, Campus Jeronimos 135, Guadalupe 30107, Spain

[3] Univ Montpellier ENSCM, IBMM, Fac Pharm, UMR 5247,CNRS, F-34093 Montpellier, France

[4] Univ Campus Espinardo, Dept Food Sci & Technol, Res Grp Qual Safety & Bioact Plant Foods, CEBAS CSIC, Edif 25, Espinardo 30100, Spain

[5] Univ Catolica Murcia UCAM, Hlth Sci Dept, Mol Recognit & Encapsulat Res Grp REM, Campus Jeronimos 135, Guadalupe 30107, Spain

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 03期

关键词：

phytoprostanes; prostaglandins; platelets; EP3; receptor; migration; inflammation; UHPLC-QQQ-MS/MS; PROCESSING CONDITIONS; AGGREGATION; INHIBITION; MONOCYTES; ACCURACY; DOCKING; PROFILE; IMPACT;

D O I：

10.3390/ijms24032730

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Gracilaria longissima, 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(2). 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-2 (PGE(2)), 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(2) main target receptor in platelets suggest herein that this oxylipin could be a strong candidate for pharmaceutical research from a multitarget perspective.

引用

页数：16