A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>α
Phospholipase A<sub>2</sub>s constitute a wide group of lipid-modifying enzymes which display a variety of functions in innate immune responses. In this work, we utilized mass spectrometry-based lipidomic approaches to investigate the action of Asp-49 Ca<sup>2+</sup>-dependen...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/10/6/891 |
| _version_ | 1797565635626008576 |
|---|---|
| author | Juan P. Rodríguez Elbio Leiguez Carlos Guijas Bruno Lomonte José M. Gutiérrez Catarina Teixeira María A. Balboa Jesús Balsinde |
| author_facet | Juan P. Rodríguez Elbio Leiguez Carlos Guijas Bruno Lomonte José M. Gutiérrez Catarina Teixeira María A. Balboa Jesús Balsinde |
| author_sort | Juan P. Rodríguez |
| collection | DOAJ |
| description | Phospholipase A<sub>2</sub>s constitute a wide group of lipid-modifying enzymes which display a variety of functions in innate immune responses. In this work, we utilized mass spectrometry-based lipidomic approaches to investigate the action of Asp-49 Ca<sup>2+</sup>-dependent secreted phospholipase A<sub>2</sub> (sPLA<sub>2</sub>) (MT-III) and Lys-49 sPLA2 (MT-II), two group IIA phospholipase A<sub>2</sub>s isolated from the venom of the snake <i>Bothrops asper</i>, on human peripheral blood monocytes. MT-III is catalytically active, whereas MT-II lacks enzyme activity. A large decrease in the fatty acid content of membrane phospholipids was detected in MT III-treated monocytes. The significant diminution of the cellular content of phospholipid-bound arachidonic acid seemed to be mediated, in part, by the activation of the endogenous group IVA cytosolic phospholipase A<sub>2</sub>α. MT-III triggered the formation of triacylglycerol and cholesterol enriched in palmitic, stearic, and oleic acids, but not arachidonic acid, along with an increase in lipid droplet synthesis. Additionally, it was shown that the increased availability of arachidonic acid arising from phospholipid hydrolysis promoted abundant eicosanoid synthesis. The inactive form, MT-II, failed to produce any of the effects described above. These studies provide a complete lipidomic characterization of the monocyte response to snake venom group IIA phospholipase A<sub>2</sub>, and reveal significant connections among lipid droplet biogenesis, cell signaling and biochemical pathways that contribute to initiating the inflammatory response. |
| first_indexed | 2024-03-10T19:14:53Z |
| format | Article |
| id | doaj.art-4c4ca2738c5f424e8d241d2b58dc3cb8 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T19:14:53Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-4c4ca2738c5f424e8d241d2b58dc3cb82023-11-20T03:27:48ZengMDPI AGBiomolecules2218-273X2020-06-0110689110.3390/biom10060891A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>αJuan P. Rodríguez0Elbio Leiguez1Carlos Guijas2Bruno Lomonte3José M. Gutiérrez4Catarina Teixeira5María A. Balboa6Jesús Balsinde7Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501–2060, Costa RicaInstituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501–2060, Costa RicaLaboratorio de Farmacologia, Instituto Butantan, Sao Paulo 01000, BrazilInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainInstituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, SpainPhospholipase A<sub>2</sub>s constitute a wide group of lipid-modifying enzymes which display a variety of functions in innate immune responses. In this work, we utilized mass spectrometry-based lipidomic approaches to investigate the action of Asp-49 Ca<sup>2+</sup>-dependent secreted phospholipase A<sub>2</sub> (sPLA<sub>2</sub>) (MT-III) and Lys-49 sPLA2 (MT-II), two group IIA phospholipase A<sub>2</sub>s isolated from the venom of the snake <i>Bothrops asper</i>, on human peripheral blood monocytes. MT-III is catalytically active, whereas MT-II lacks enzyme activity. A large decrease in the fatty acid content of membrane phospholipids was detected in MT III-treated monocytes. The significant diminution of the cellular content of phospholipid-bound arachidonic acid seemed to be mediated, in part, by the activation of the endogenous group IVA cytosolic phospholipase A<sub>2</sub>α. MT-III triggered the formation of triacylglycerol and cholesterol enriched in palmitic, stearic, and oleic acids, but not arachidonic acid, along with an increase in lipid droplet synthesis. Additionally, it was shown that the increased availability of arachidonic acid arising from phospholipid hydrolysis promoted abundant eicosanoid synthesis. The inactive form, MT-II, failed to produce any of the effects described above. These studies provide a complete lipidomic characterization of the monocyte response to snake venom group IIA phospholipase A<sub>2</sub>, and reveal significant connections among lipid droplet biogenesis, cell signaling and biochemical pathways that contribute to initiating the inflammatory response.https://www.mdpi.com/2218-273X/10/6/891phospholipase A<sub>2</sub>lipidomicsmass spectrometrylipid signalinginflammationmonocytes/macrophages |
| spellingShingle | Juan P. Rodríguez Elbio Leiguez Carlos Guijas Bruno Lomonte José M. Gutiérrez Catarina Teixeira María A. Balboa Jesús Balsinde A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>α Biomolecules phospholipase A<sub>2</sub> lipidomics mass spectrometry lipid signaling inflammation monocytes/macrophages |
| title | A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>α |
| title_full | A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>α |
| title_fullStr | A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>α |
| title_full_unstemmed | A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>α |
| title_short | A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A<sub>2</sub> on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A<sub>2</sub>α |
| title_sort | lipidomic perspective of the action of group iia secreted phospholipase a sub 2 sub on human monocytes lipid droplet biogenesis and activation of cytosolic phospholipase a sub 2 sub α |
| topic | phospholipase A<sub>2</sub> lipidomics mass spectrometry lipid signaling inflammation monocytes/macrophages |
| url | https://www.mdpi.com/2218-273X/10/6/891 |
| work_keys_str_mv | AT juanprodriguez alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT elbioleiguez alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT carlosguijas alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT brunolomonte alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT josemgutierrez alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT catarinateixeira alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT mariaabalboa alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT jesusbalsinde alipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT juanprodriguez lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT elbioleiguez lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT carlosguijas lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT brunolomonte lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT josemgutierrez lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT catarinateixeira lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT mariaabalboa lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba AT jesusbalsinde lipidomicperspectiveoftheactionofgroupiiasecretedphospholipaseasub2subonhumanmonocyteslipiddropletbiogenesisandactivationofcytosolicphospholipaseasub2suba |