Caged ceramide 1-phosphate (C1P) analogs: Novel tools for studying C1P biology. (January 2016)

• Record Type: Journal Article
• Authors: Gomez-Muñoz, Antonio; Gangoiti, Patricia; Rivera, Io-Guané; Presa, Natalia; Gomez-Larrauri, Ana; Ordoñez, Marta
• Is Part Of: Chemistry and physics of lipids. Volume 194:(2016)
• Page Start: 79
• Page End: 84
• Publication Date: 2016-01
• Subjects: Akt (PKB) protein kinase -- B BHNB 4-bromo-5-hydroxy-2-nitrobenzhydryl -- BMDM bone marrow-derived macrophages -- CerK ceramide kinase -- C1P ceramide 1-phosphate -- cPLA2 calcium-dependent cytosolic phospholipase 2 -- DECM 7-(N, N-diethylamino)coumarin -- ERK extracellularly regulated kinases -- GLUT glucose transporter -- iNOS inducible nitric oxide synthase -- PKC protein kinase C -- PI3K phosphatidylinositol 3-kinase -- PTX pertussis toxin -- ROS reacfive oxygen species -- SMase sphingomyelinase -- SPT serine palmitoyl transferase; Caged lipids -- Ceramides -- Ceramide 1-phosphate -- Photolysis -- Sphingolipids; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2015.07.019
• Languages: English
• ISSNs: 0009-3084

Abstract

Highlights: Ceramide 1-phosphate (C1P) regulates cell growth, survival and cell migration. C1P is involved in inflammatory responses. Endogenous C1P binds cPLA2, acid sphingomyelinase, and serine palmitoyltransferase. Exogenous C1P binds an unidentified Gi protein-coupled receptor and annexin a2-p11. Abstract: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid metabolite that is produced in cells by the action of ceramide kinase (CerK) acting upon ceramide, and is also found in the circulation. C1P was first demonstrated to be mitogenic and antiapoptotic in different cell types, and was later shown to induce cell migration. Understanding the precise mechanisms by which C1P exerts its biological effects has been possible using specific photosensitive caged C1P analogues synthesized by Robert Bittman's group. These compounds are cell permeable, bypass cell plasma membrane receptors, and can be released into the cytosol upon light irradiation, thereby allowing precise determination of the intracellular mechanisms of actions of C1P. Two derivatives of N -palmitoyl-ceramide 1-phosphate have been used in most studies. In one C1P derivative the cage was 7-( N, N -diethylamino)coumarin (DECM-C1P) while in the other it was a 4-bromo-5-hydroxy-2-nitrobenzhydryl moiety (BHNB-C1P). The uncaging process released C1P in the cytosol, and this was accompanied by stimulation of cell proliferation, inhibition of apoptosis, and production of low levels of reactive oxygen species. However, intracellular accumulation of C1P did not affect chemotaxis. The caged C1P analogues allowed distinction between the extracellular events evoked by C1P, as for example through interaction with a putative cell-surface receptor, from its intracellular effects.