Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma
Phospholipids containing oxidized esterified PUFA residues (OxPLs) are increasingly recognized for multiple biological activities and causative involvement in disease pathogenesis. Pharmacokinetics of these compounds in blood plasma is essentially not studied. Human plasma contains both genuine phos...
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Elsevier
2025-02-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227525000021 |
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| author | Philipp Jokesch Olga Oskolkova Maria Fedorova Bernd Gesslbauer Valery Bochkov |
| author_facet | Philipp Jokesch Olga Oskolkova Maria Fedorova Bernd Gesslbauer Valery Bochkov |
| author_sort | Philipp Jokesch |
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| description | Phospholipids containing oxidized esterified PUFA residues (OxPLs) are increasingly recognized for multiple biological activities and causative involvement in disease pathogenesis. Pharmacokinetics of these compounds in blood plasma is essentially not studied. Human plasma contains both genuine phospholipases A2 [platelet activating factor acetyl hydrolase (PAF-AH) (also called Lp-PLA2) and secretory phospholipase A2] and multifunctional enzymes capable of removing sn-2 residues in native and oxidized PLs (lecithin-cholesterol acyltransferase, peroxiredoxin-6). The goal of this study was to compare relative activities of different PLA2 enzymes by analyzing cleavage of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylcholine (OxPAPC) and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylethanolamine (OxPAPE) by diluted plasma in the presence of enzyme inhibitors. We have found that human plasma demonstrated high total PLA2 activity against oxidized PCs and PEs. PAF-AH/Lp-PLA2 played a dominant role in LysoPC and LysoPE production as compared to other enzymes. Molecular species of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylcholine and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylethanolamine could be divided into three groups according to their degradation rate and sensitivity to PAF-AH/Lp-PLA2 inhibitor darapladib. Oxidatively truncated species were most rapidly metabolized in the presence of plasma; this process was strongly inhibited by darapladib. The rate of degradation of full-length OxPLs depended on the degree of oxygenation. Species containing 1 to 3 oxygen atoms were relatively stable to degradation in plasma, while OxPLs containing > 3 extra oxygens were degraded but at significantly slower rate than truncated species. In contrast to truncated species, degradation of full-length OxPLs with > 3 extra oxygens were only minimally inhibited by darapladib. These data provide further insights into the mechanisms regulating circulating levels of OxPLs and lipid mediators generated by PLA2 cleavage of OxPLs, namely oxylipins and LysoPC. |
| format | Article |
| id | doaj-art-7739061321b547dd998a3ed825f75126 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-7739061321b547dd998a3ed825f751262025-02-02T05:26:36ZengElsevierJournal of Lipid Research0022-22752025-02-01662100742Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasmaPhilipp Jokesch0Olga Oskolkova1Maria Fedorova2Bernd Gesslbauer3Valery Bochkov4Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Graz, AustriaInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Graz, AustriaCenter of Membrane Biochemistry and Lipid Research, University Hospital Carl Gustav Carus and Faculty of Medicine of TU Dresden, Dresden, GermanyInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Graz, Austria; For correspondence: Valery Bochkov; Bernd GesslbauerInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Graz, Austria; Field of Excellence BioHealth - University of Graz, Graz, Austria; For correspondence: Valery Bochkov; Bernd GesslbauerPhospholipids containing oxidized esterified PUFA residues (OxPLs) are increasingly recognized for multiple biological activities and causative involvement in disease pathogenesis. Pharmacokinetics of these compounds in blood plasma is essentially not studied. Human plasma contains both genuine phospholipases A2 [platelet activating factor acetyl hydrolase (PAF-AH) (also called Lp-PLA2) and secretory phospholipase A2] and multifunctional enzymes capable of removing sn-2 residues in native and oxidized PLs (lecithin-cholesterol acyltransferase, peroxiredoxin-6). The goal of this study was to compare relative activities of different PLA2 enzymes by analyzing cleavage of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylcholine (OxPAPC) and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylethanolamine (OxPAPE) by diluted plasma in the presence of enzyme inhibitors. We have found that human plasma demonstrated high total PLA2 activity against oxidized PCs and PEs. PAF-AH/Lp-PLA2 played a dominant role in LysoPC and LysoPE production as compared to other enzymes. Molecular species of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylcholine and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphatidylethanolamine could be divided into three groups according to their degradation rate and sensitivity to PAF-AH/Lp-PLA2 inhibitor darapladib. Oxidatively truncated species were most rapidly metabolized in the presence of plasma; this process was strongly inhibited by darapladib. The rate of degradation of full-length OxPLs depended on the degree of oxygenation. Species containing 1 to 3 oxygen atoms were relatively stable to degradation in plasma, while OxPLs containing > 3 extra oxygens were degraded but at significantly slower rate than truncated species. In contrast to truncated species, degradation of full-length OxPLs with > 3 extra oxygens were only minimally inhibited by darapladib. These data provide further insights into the mechanisms regulating circulating levels of OxPLs and lipid mediators generated by PLA2 cleavage of OxPLs, namely oxylipins and LysoPC.http://www.sciencedirect.com/science/article/pii/S0022227525000021oxidized lipidsphospholipases/A2phospholipidsglycerophospholipidslipidomicsglycerophospholipid cleavage |
| spellingShingle | Philipp Jokesch Olga Oskolkova Maria Fedorova Bernd Gesslbauer Valery Bochkov Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma Journal of Lipid Research oxidized lipids phospholipases/A2 phospholipids glycerophospholipids lipidomics glycerophospholipid cleavage |
| title | Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma |
| title_full | Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma |
| title_fullStr | Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma |
| title_full_unstemmed | Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma |
| title_short | Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma |
| title_sort | contribution of individual phospholipase a2 enzymes to the cleavage of oxidized phospholipids in human blood plasma |
| topic | oxidized lipids phospholipases/A2 phospholipids glycerophospholipids lipidomics glycerophospholipid cleavage |
| url | http://www.sciencedirect.com/science/article/pii/S0022227525000021 |
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