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Dihydroceramide desaturase inhibition by a cyclopropanated dihydroceramide analog in cultured keratinocytes.

Brodesser S, Kolter T - J Lipids (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: CECAD Cologne Platform Lipidomics, Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany.

ABSTRACT
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.

No MeSH data available.


Effect of 1 on transcription levels of differentiation markers and enzymes of sphingolipid metabolism in cultured human keratinocytes. Proliferating cells were incubated with 50 μM of 1 for 24 h and were then submitted to a calcium shift to induce differentiation.
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fig2: Effect of 1 on transcription levels of differentiation markers and enzymes of sphingolipid metabolism in cultured human keratinocytes. Proliferating cells were incubated with 50 μM of 1 for 24 h and were then submitted to a calcium shift to induce differentiation.

Mentions: In order to investigate functional consequences of the reduction of newly biosynthesized unsaturated sphingolipids brought about by 1, we quantified the mRNA levels of several proteins involved in cell differentiation and ceramide metabolism by real-time polymerase chain reaction (Figure 2).


Dihydroceramide desaturase inhibition by a cyclopropanated dihydroceramide analog in cultured keratinocytes.

Brodesser S, Kolter T - J Lipids (2010)

Effect of 1 on transcription levels of differentiation markers and enzymes of sphingolipid metabolism in cultured human keratinocytes. Proliferating cells were incubated with 50 μM of 1 for 24 h and were then submitted to a calcium shift to induce differentiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066699&req=5

fig2: Effect of 1 on transcription levels of differentiation markers and enzymes of sphingolipid metabolism in cultured human keratinocytes. Proliferating cells were incubated with 50 μM of 1 for 24 h and were then submitted to a calcium shift to induce differentiation.
Mentions: In order to investigate functional consequences of the reduction of newly biosynthesized unsaturated sphingolipids brought about by 1, we quantified the mRNA levels of several proteins involved in cell differentiation and ceramide metabolism by real-time polymerase chain reaction (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: CECAD Cologne Platform Lipidomics, Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany.

ABSTRACT
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.

No MeSH data available.