Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial Cells
Oxidized phospholipids (OxPLs) are generated by enzymatic or autooxidation of esterified polyunsaturated fatty acids (PUFAs) residues. OxPLs are present in circulation and atherosclerotic plaques where they are thought to induce predominantly proinflammatory and toxic changes in endothelial (ECs) an...
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MDPI AG
2022-09-01
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| Series: | Antioxidants |
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| author | Christina Mauerhofer Taras Afonyushkin Olga V. Oskolkova Klara Hellauer Bernd Gesslbauer Jasmin Schmerda Yunbo Ke Andreas Zimmer Anna A. Birukova Konstantin G. Birukov Valery Bochkov |
| author_facet | Christina Mauerhofer Taras Afonyushkin Olga V. Oskolkova Klara Hellauer Bernd Gesslbauer Jasmin Schmerda Yunbo Ke Andreas Zimmer Anna A. Birukova Konstantin G. Birukov Valery Bochkov |
| author_sort | Christina Mauerhofer |
| collection | DOAJ |
| description | Oxidized phospholipids (OxPLs) are generated by enzymatic or autooxidation of esterified polyunsaturated fatty acids (PUFAs) residues. OxPLs are present in circulation and atherosclerotic plaques where they are thought to induce predominantly proinflammatory and toxic changes in endothelial (ECs) and other cell types. Unexpectedly, we found that low concentrations of OxPLs were not toxic but protected ECs from stress induced by serum deprivation or cytostatic drugs. The protective effect was observed in ECs obtained from different vessels and was monitored using a variety of readouts based on different biological and chemical principles. Analysis of the structure–activity relationship identified oxidized or missing fatty acid residue (OxPLs or Lyso-PLs, respectively) as a prerequisite for the protective action of a PL. Protective OxPLs or Lyso-PLs acquired detergent-like properties and formed in solution aggregates <10 nm in diameter (likely micelles), which were in striking contrast with large aggregates (>1000 nm, likely multilayer liposomes) produced by nonoxidized precursor PLs. Because surfactants, OxPLs, and Lyso-PLs are known to extract membrane cholesterol, we tested if this effect might trigger the protection of endothelial cells. The protective action of OxPLs and Lyso-PLs was inhibited by cotreatment with cholesterol and mimicked by cholesterol-binding beta-cyclodextrin but not inactive α-cyclodextrin. Wide-scale mRNA expression analysis in four types of ECs showed the induction of genes encoding for heat shock proteins (HSPs) and secreted prosurvival peptides and proteins. Inducers of HSPs, chemical chaperones, and pure prosurvival factors mimicked the protective action of OxPLs/Lyso-PLs. We hypothesize that oxidation changes the physicochemical properties of PLs, thus promoting membrane cholesterol redistribution or extraction leading to the expression of intra- and extracellular prosurvival factors. |
| first_indexed | 2024-03-10T00:53:07Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T00:53:07Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-9f9c42961f1b4566b0ce29ef2828cc2e2023-11-23T14:48:11ZengMDPI AGAntioxidants2076-39212022-09-01119174110.3390/antiox11091741Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial CellsChristina Mauerhofer0Taras Afonyushkin1Olga V. Oskolkova2Klara Hellauer3Bernd Gesslbauer4Jasmin Schmerda5Yunbo Ke6Andreas Zimmer7Anna A. Birukova8Konstantin G. Birukov9Valery Bochkov10Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, AustriaDepartment of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, AustriaInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, AustriaInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, AustriaInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, AustriaInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, AustriaDepartment of Anesthesiology, University of Maryland School of Medicine, 20 Penn. Street, HSF-2, Room 145, Baltimore, MD 21201, USAInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, University of Graz, Universitätsplatz 1/EG, 8010 Graz, AustriaDepartment of Anesthesiology, University of Maryland School of Medicine, 20 Penn. Street, HSF-2, Room 145, Baltimore, MD 21201, USADepartment of Anesthesiology, University of Maryland School of Medicine, 20 Penn. Street, HSF-2, Room 145, Baltimore, MD 21201, USAInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, AustriaOxidized phospholipids (OxPLs) are generated by enzymatic or autooxidation of esterified polyunsaturated fatty acids (PUFAs) residues. OxPLs are present in circulation and atherosclerotic plaques where they are thought to induce predominantly proinflammatory and toxic changes in endothelial (ECs) and other cell types. Unexpectedly, we found that low concentrations of OxPLs were not toxic but protected ECs from stress induced by serum deprivation or cytostatic drugs. The protective effect was observed in ECs obtained from different vessels and was monitored using a variety of readouts based on different biological and chemical principles. Analysis of the structure–activity relationship identified oxidized or missing fatty acid residue (OxPLs or Lyso-PLs, respectively) as a prerequisite for the protective action of a PL. Protective OxPLs or Lyso-PLs acquired detergent-like properties and formed in solution aggregates <10 nm in diameter (likely micelles), which were in striking contrast with large aggregates (>1000 nm, likely multilayer liposomes) produced by nonoxidized precursor PLs. Because surfactants, OxPLs, and Lyso-PLs are known to extract membrane cholesterol, we tested if this effect might trigger the protection of endothelial cells. The protective action of OxPLs and Lyso-PLs was inhibited by cotreatment with cholesterol and mimicked by cholesterol-binding beta-cyclodextrin but not inactive α-cyclodextrin. Wide-scale mRNA expression analysis in four types of ECs showed the induction of genes encoding for heat shock proteins (HSPs) and secreted prosurvival peptides and proteins. Inducers of HSPs, chemical chaperones, and pure prosurvival factors mimicked the protective action of OxPLs/Lyso-PLs. We hypothesize that oxidation changes the physicochemical properties of PLs, thus promoting membrane cholesterol redistribution or extraction leading to the expression of intra- and extracellular prosurvival factors.https://www.mdpi.com/2076-3921/11/9/1741oxidized phospholipidsendothelial cell stresscell survival |
| spellingShingle | Christina Mauerhofer Taras Afonyushkin Olga V. Oskolkova Klara Hellauer Bernd Gesslbauer Jasmin Schmerda Yunbo Ke Andreas Zimmer Anna A. Birukova Konstantin G. Birukov Valery Bochkov Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial Cells Antioxidants oxidized phospholipids endothelial cell stress cell survival |
| title | Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial Cells |
| title_full | Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial Cells |
| title_fullStr | Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial Cells |
| title_full_unstemmed | Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial Cells |
| title_short | Low Concentrations of Oxidized Phospholipids Increase Stress Tolerance of Endothelial Cells |
| title_sort | low concentrations of oxidized phospholipids increase stress tolerance of endothelial cells |
| topic | oxidized phospholipids endothelial cell stress cell survival |
| url | https://www.mdpi.com/2076-3921/11/9/1741 |
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