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Journal of Lipids
Volume 2011 (2011), Article ID 724015, 9 pages
Research Article

Dihydroceramide Desaturase Inhibition by a Cyclopropanated Dihydroceramide Analog in Cultured Keratinocytes

1CECAD Cologne Platform Lipidomics, Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany
2LIMES Program Unit Membrane Biology and Lipid Biochemistry, Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany

Received 1 July 2010; Revised 21 September 2010; Accepted 27 October 2010

Academic Editor: Michel Lagarde

Copyright © 2011 Susanne Brodesser and Thomas Kolter. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Most mammalian sphingolipids contain a 4,5-(E)-double bond. We report on the chemical synthesis of a dihydroceramide derivative that prevents the introduction of the double bond into sphingolipids. Minimal alteration of the parent structure by formally replacing the hydrogen atoms in the 5- and in the 6-position of the sphinganine backbone by a methylene group leads to an inhibitor of dihydroceramide desaturase in cultured cells. In the presence of 10–50 μM of compound (1), levels of biosynthetically formed dihydroceramide and—surprisingly—also of phytoceramide are elevated at the expense of ceramide. The cells respond to the lack of unsaturated sphingolipids by an elevation of mRNAs of enzymes required for sphingosine formation. At the same time, the analysis of proliferation and differentiation markers indicates that the sphingolipid double bond is required to keep the cells in a differentiated state.