Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation
Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a...
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MDPI AG
2015-04-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/7/5/1457 |
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| author | Io-Guané Rivera Marta Ordoñez Natalia Presa Ana Gomez-Larrauri Jorge Simón Miguel Trueba Antonio Gomez-Muñoz |
| author_facet | Io-Guané Rivera Marta Ordoñez Natalia Presa Ana Gomez-Larrauri Jorge Simón Miguel Trueba Antonio Gomez-Muñoz |
| author_sort | Io-Guané Rivera |
| collection | DOAJ |
| description | Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type) sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation. Interestingly, the venom of some arthropodes including spiders of the genus Loxosceles, or the toxins of some bacteria such as Corynebacterium tuberculosis, or Vibrio damsela possess high levels of D-type sphingomyelinase (SMase D). This enzyme catalyzes the hydrolysis of SM to yield ceramide 1-phosphate (C1P), which promotes cell growth and survival and is a potent pro-inflammatory agent in different cell types. In particular, C1P stimulates cytosolic phospholipase A2 leading to arachidonic acid release and the subsequent formation of eicosanoids, actions that are all associated to the promotion of inflammation. In addition, C1P potently stimulates macrophage migration, which has also been associated to inflammatory responses. Interestingly, this action required the interaction of C1P with a specific plasma membrane receptor, whereas accumulation of intracellular C1P failed to stimulate chemotaxis. The C1P receptor is coupled to Gi proteins and activates of the PI3K/Akt and MEK/ERK1-2 pathways upon ligation with C1P. The proposed review will address novel aspects on the control of inflammatory responses by C1P and will highlight the molecular mechanisms whereby C1P exerts these actions. |
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| language | English |
| last_indexed | 2024-04-14T06:41:14Z |
| publishDate | 2015-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-a814046515284cb69e582d559a9834f02022-12-22T02:07:19ZengMDPI AGToxins2072-66512015-04-01751457146610.3390/toxins7051457toxins7051457Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and InflammationIo-Guané Rivera0Marta Ordoñez1Natalia Presa2Ana Gomez-Larrauri3Jorge Simón4Miguel Trueba5Antonio Gomez-Muñoz6Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, SpainSphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type) sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation. Interestingly, the venom of some arthropodes including spiders of the genus Loxosceles, or the toxins of some bacteria such as Corynebacterium tuberculosis, or Vibrio damsela possess high levels of D-type sphingomyelinase (SMase D). This enzyme catalyzes the hydrolysis of SM to yield ceramide 1-phosphate (C1P), which promotes cell growth and survival and is a potent pro-inflammatory agent in different cell types. In particular, C1P stimulates cytosolic phospholipase A2 leading to arachidonic acid release and the subsequent formation of eicosanoids, actions that are all associated to the promotion of inflammation. In addition, C1P potently stimulates macrophage migration, which has also been associated to inflammatory responses. Interestingly, this action required the interaction of C1P with a specific plasma membrane receptor, whereas accumulation of intracellular C1P failed to stimulate chemotaxis. The C1P receptor is coupled to Gi proteins and activates of the PI3K/Akt and MEK/ERK1-2 pathways upon ligation with C1P. The proposed review will address novel aspects on the control of inflammatory responses by C1P and will highlight the molecular mechanisms whereby C1P exerts these actions.http://www.mdpi.com/2072-6651/7/5/1457cell survivalcell migrationceramidesceramide 1-phosphateloxoscelisminflammationsphingolipidssphingomyelin D |
| spellingShingle | Io-Guané Rivera Marta Ordoñez Natalia Presa Ana Gomez-Larrauri Jorge Simón Miguel Trueba Antonio Gomez-Muñoz Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation Toxins cell survival cell migration ceramides ceramide 1-phosphate loxoscelism inflammation sphingolipids sphingomyelin D |
| title | Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation |
| title_full | Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation |
| title_fullStr | Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation |
| title_full_unstemmed | Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation |
| title_short | Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation |
| title_sort | sphingomyelinase d ceramide 1 phosphate in cell survival and inflammation |
| topic | cell survival cell migration ceramides ceramide 1-phosphate loxoscelism inflammation sphingolipids sphingomyelin D |
| url | http://www.mdpi.com/2072-6651/7/5/1457 |
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