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Utilization of Caged Ceramide and Ceramide 1-Phosphate Analogs for Monitoring Cellular Events after Photoactivation

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Bioactive Sphingolipids in Cancer Biology and Therapy

Abstract

Caged compounds possess a photolabile covalent bond. This chapter reviews studies of caged derivatives of two important sphingolipid signaling molecules, ceramide and ceramide 1-phosphate. Biophysical studies were carried out after a 6-bromo-7-hydroxycoumarinyl-ceramide conjugate was inserted into model bilayer membranes. Uncaging with long-wavelength UV light liberated N-palmitoylceramide, and reorganization of lipid domains in the bilayer was monitored. Two derivatives of N-palmitoyl-ceramide 1-phosphate in which the phosphate group was esterified to a caging group were investigated in macrophages; in one derivative the cage is 7-(N,N-diethylamino)coumarin (DECM-C1P)while in the other it is a 4-bromo-5-hydroxy-2-nitrobenzhydryl moiety (BHNB-C1P). The caged derivatives were delivered to macrophages in aqueous solution. The photolytic uncaging process then released ceramide 1-phosphate in the cytosol of macrophages, which was accompanied by stimulation of macrophage proliferation, reactive oxygen species production, and other intracellular signaling events. A distinction can thus be made in some cells between extracellular events evoked by ceramide 1-phosphate, as for example by its interaction with a putative cell-surface receptor, from its intracellular bioactivities. These studies show that elevation of ceramide or ceramide 1-phosphate levels by uncaging of their inactive caged forms enable investigations of a wide variety of biophysical and biochemical processes.

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Acknowledegements

We are grateful for financial support of the work with caged Cer and caged C1P from the National Institutes of Health (Grant HL-083187 to R.B.) and Grants IT-705-13 from the Departamento de EducaciĂłn, Universidades e InvestigaciĂłn del Gobierno Vasco (Gazteiz-Vitoria, Basque Country), and S-PE13UN017 from Departamento de Industria, Comercio y Turismo del Gobierno Vasco (Gazteiz-Vitoria, Basque Country) (to A. G. M.).

We are indebted to Dr. Patricia Gangoiti for providing Fig. 6. We also thank our many collaborators, especially Dr. Linda J. Johnston, Dr. Daniel M. Carter Ramirez, Dr. Young Ah Kim, and Dr. Ravi S. Lankalapalli, who worked with us on the caged ceramide and caged ceramide 1-phosphate projects.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, NY, 11367, USA

    Robert Bittman

  2. Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 644, Bilbao, 48080, Spain

    Antonio Gomez-Muñoz

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  1. Robert Bittman
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  2. Antonio Gomez-Muñoz
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Correspondence to Robert Bittman .

Editor information

Editors and Affiliations

  1. Stony Brook University, Stony Brook Cancer Center, Stony Brook, New York, USA

    Yusuf A. Hannun

  2. Dept. of Physiology & Biophysics, Stony Brook University, Stony Brook, New York, USA

    Chiara Luberto

  3. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

    Cungui Mao

  4. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

    Lina Marie Obeid

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Bittman, R., Gomez-Muñoz, A. (2015). Utilization of Caged Ceramide and Ceramide 1-Phosphate Analogs for Monitoring Cellular Events after Photoactivation. In: Hannun, Y., Luberto, C., Mao, C., Obeid, L. (eds) Bioactive Sphingolipids in Cancer Biology and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-20750-6_17

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