Academic Journal
Oxidized phospholipids on alkyl-amide scaffold demonstrate anti-endotoxin and endothelial barrier-protective properties
| العنوان: | Oxidized phospholipids on alkyl-amide scaffold demonstrate anti-endotoxin and endothelial barrier-protective properties |
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| المؤلفون: | Oskolkova, Olga, V, Hodzic, Alma, Karki, Pratap, Gesslbauer, Bernd, Ke, Yunbo, Hofer, Dina, C, Bogner-Strauss, Juliane, G, Galano, Jean-Marie, Oger, Camille, Birukova, Anna, Durand, Thierry, Birukov, Konstantin, Bochkov, Valery |
| المساهمون: | Karl-Franzens-Universität Graz, University of Maryland School of Medicine, University of Maryland System, Graz University of Technology Graz (TU Graz), Institut des Biomolécules Max Mousseron Pôle Chimie Balard (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 0891-5849 ; Free Radical Biology and Medicine ; https://hal.umontpellier.fr/hal-03378766 ; Free Radical Biology and Medicine, 2021, 174, pp.264 - 271. ⟨10.1016/j.freeradbiomed.2021.07.041⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2021 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | Oxidized phospholipids, Synthesis, Lipopolysaccharide, Lung endothelial barrier, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology |
| الوصف: | International audience ; Oxidized phospholipids (OxPLs) containing enzymatically or non-enzymatically oxidized fatty acids (oxylipins) are increasingly recognized as lipid mediators involved in pathogenesis of diseases. Further understanding of structure-activity relationship and molecular mechanisms activated by OxPLs is hampered by the complexity of synthesis of individual molecular species. Although dozens of individual free oxylipins are commercially available, their attachment to the phospholipid scaffold requires relatively harsh conditions during activation of carboxy-group, which may lead to decomposition of unstable oxylipins. Furthermore, additional protection-deprotection steps are required for oxylipins containing hydroxy-groups. In this work we describe synthesis of OxPLs containing oxylipins bound at the sn-2-position via an amide-bond that is characteristic of sphingophospholipids. Activation of oxylipins and attachment to the phospholipid scaffold are performed under mild conditions and characterized by high yield. Hydroxy-groups of oxylipins do not interfere with reactions and therefore no protection/deprotection steps are needed. In order to prevent oxylipin migration, a fatty acid residue at the sn-1 was bound through an alkyl bond, which is a common bond present in a large proportion of naturally occurring phospholipids. An additional advantage of combining alkyl and amide bonds in a single phospholipid molecule is that both types of bonds are phospholipase A1/A2-resistant, which may be expected to improve biological stability of OxPLs and thus simplify analysis of their effects. As proof of principle, several alkyl-amide oxidized phosphatidylcholines (OxPCs) containing either linear or prostane ring oxylipins have been synthesized. Importantly, we show here that alkyl-amide-OxPCs demonstrated biological activities similar to those of di-acyl-OxPCs. Alkyl-amide-OxPCs inhibited pro-inflammatory action of LPS and increased endothelial cellular barrier in vitro and in mouse models. The effects ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-03378766; https://hal.umontpellier.fr/hal-03378766; https://hal.umontpellier.fr/hal-03378766/document; https://hal.umontpellier.fr/hal-03378766/file/1-s2.0-S0891584921004408-main.pdf |
| DOI: | 10.1016/j.freeradbiomed.2021.07.041 |
| الاتاحة: | https://hal.umontpellier.fr/hal-03378766 https://hal.umontpellier.fr/hal-03378766/document https://hal.umontpellier.fr/hal-03378766/file/1-s2.0-S0891584921004408-main.pdf https://doi.org/10.1016/j.freeradbiomed.2021.07.041 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.E81A240C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.freeradbiomed.2021.07.041 |
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