? ? The goal of this resource is to synthesize a wide range of variants of sphingosine 1-phosphate (S1P), sphingomyelin, and glycosphingolipids that will be made available for collaborations with NHLBI and other investigators whose studies are pertinent to cardiovascular and lung biology. The analogs to be prepared include phosphonate and photoaffinity probes of S1P and FTY720-phosphate, an immunosuppressive prodrug that, like S1P, is produced by sphingosine kinases and then targets specific plasma membrane receptors. This application describes eighteen projects that will be facilitated by access to unique sphingolipids. The objectives of some of these projects include the identification of the ligand-binding pocket of the receptors of S1P, psychosine, and sphingosylphosphocholine. Other goals include the elucidation of the molecular mechanisms responsible for: modulation of T lymphocyte functions and of infection-mediated inflammatory responses in the lung by S1P and FTY720; cardioprotection by sphingolipid phosphate analogs; deformation-induced lipid trafficking in alveolar epithelial cells; inhibition of lipolytic activity and lipid peroxidation by sphingomyelin; alteration of the transbilayer asymmetry of glycosphingolipids by sphingomyelin; and internalization of glycosphingolipids by a caveolar-dependent pathway in living epithelial cells. Finally, the sphingoid backbone or fatty acyl chain of sphingolipids will be labeled with deuterium at specific sites to probe sphingolipid interactions with other membrane lipids and for use as internal standards in stable-isotope dilution assays. This research seeks to enhance our understanding of lipids that have unique effects in cardiovascular and lung biology. Specialized lipids will be prepared and used in experiments that will provide much-needed data about the properties of these lipids, leading to the development of long-acting compounds to protect against lung injury and cardiac damage. (End of Abstract) ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Resource-Related Research Projects (R24)
Project #
5R24HL083187-02
Application #
7175491
Study Section
Special Emphasis Panel (ZHL1-CSR-H (O2))
Program Officer
Srinivas, Pothur R
Project Start
2006-02-06
Project End
2011-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
2
Fiscal Year
2007
Total Cost
$373,835
Indirect Cost
Name
Queens College
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
619346146
City
Flushing
State
NY
Country
United States
Zip Code
11367
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Carter Ramirez, Daniel M; Kim, Young Ah; Bittman, Robert et al. (2013) Lipid Phase Separation and Protein-Ganglioside Clustering in Supported Bilayers Are Induced by Photorelease of Ceramide. Soft Matter 9:4890-4899
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