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Toxins 2015, 7(5), 1457-1466;

Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation

Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain
Author to whom correspondence should be addressed.
Academic Editor: Azzam Maghazachi
Received: 30 March 2015 / Revised: 20 April 2015 / Accepted: 22 April 2015 / Published: 29 April 2015
(This article belongs to the Special Issue G-Protein Coupled Receptors as mediators of Toxin effects)
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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. View Full-Text
Keywords: cell survival; cell migration; ceramides; ceramide 1-phosphate; loxoscelism; inflammation; sphingolipids; sphingomyelin D cell survival; cell migration; ceramides; ceramide 1-phosphate; loxoscelism; inflammation; sphingolipids; sphingomyelin D

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Rivera, I.-G.; Ordoñez, M.; Presa, N.; Gomez-Larrauri, A.; Simón, J.; Trueba, M.; Gomez-Muñoz, A. Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation. Toxins 2015, 7, 1457-1466.

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