Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study
Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/10/2058 |
| _version_ | 1797475716712890368 |
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| author | Ali Khattib Sanaa Musa Majdi Halabi Tony Hayek Soliman Khatib |
| author_facet | Ali Khattib Sanaa Musa Majdi Halabi Tony Hayek Soliman Khatib |
| author_sort | Ali Khattib |
| collection | DOAJ |
| description | Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from <i>Nannochloropsis</i> microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation. |
| first_indexed | 2024-03-09T20:48:55Z |
| format | Article |
| id | doaj.art-c71718d82861452db49e957bcd64adda |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T20:48:55Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c71718d82861452db49e957bcd64adda2023-11-23T22:40:05ZengMDPI AGAntioxidants2076-39212022-10-011110205810.3390/antiox11102058Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship StudyAli Khattib0Sanaa Musa1Majdi Halabi2Tony Hayek3Soliman Khatib4Natural Compounds and Analytical Chemistry Laboratory, MIGAL—Galilee Research Institute, P.O. Box 831, Kiryat Shemona 11016, IsraelNatural Compounds and Analytical Chemistry Laboratory, MIGAL—Galilee Research Institute, P.O. Box 831, Kiryat Shemona 11016, IsraelZiv Medical Center, Safed 13100, IsraelThe Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa 31096, IsraelNatural Compounds and Analytical Chemistry Laboratory, MIGAL—Galilee Research Institute, P.O. Box 831, Kiryat Shemona 11016, IsraelParaoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from <i>Nannochloropsis</i> microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation.https://www.mdpi.com/2076-3921/11/10/2058lyso-DGTSparaoxonase 1dockingstructure-activity relationshipantioxidant activitiesLDL oxidation |
| spellingShingle | Ali Khattib Sanaa Musa Majdi Halabi Tony Hayek Soliman Khatib Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study Antioxidants lyso-DGTS paraoxonase 1 docking structure-activity relationship antioxidant activities LDL oxidation |
| title | Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study |
| title_full | Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study |
| title_fullStr | Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study |
| title_full_unstemmed | Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study |
| title_short | Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study |
| title_sort | lyso dgts lipid derivatives enhance pon1 activities and prevent oxidation of ldl a structure activity relationship study |
| topic | lyso-DGTS paraoxonase 1 docking structure-activity relationship antioxidant activities LDL oxidation |
| url | https://www.mdpi.com/2076-3921/11/10/2058 |
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