Sphingolipid metabolic changes during chiral C2-ceramides induced apoptosis in human leukemia cells

Archives of Pharmacal Research
M Y BaekY M Lee

Abstract

N-acetylsphingosine (C2-ceramide) is a synthetic water-soluble ceramide mimicking the activity of natural ceramides. By fixing chiral conformation on carbon numbers 2 and 3 in the ceramide structure, four chiral C2-ceramides naming d-erythro-, l-erythro-, d-threo- and l-threo C2-ceramide were synthesized. We have investigated the chiral effects of these C2-ceramides on the sphingolipid metabolism, particularly on both the sphingolipid biosynthetic pathway and on the degradation pathway. In both HL-60 and U937 cells, the chiral C2-ceramide (10 microM) showed sphingosine accumulation monitored fluoromatrically by a high performance liquid chromatographic separation of the sphingoid bases. Most importantly, in HL-60 cells, l-erythro C2-ceramide induced a 50 fold increase in sphingosine as compared to the control, while l-threo C2-ceramide exhibited a minimal 7-fold increase. In contrast, sphinganine, another sphingoid base, showed less accumulation by any chiral C2-ceramide tested under the same conditions. These results suggested that chiral C2-ceramide primarily acts on the sphingolipid degradation pathway rather than on the sphingolipid biosynthetic route. The strong G0/G1 phase arrest in the cell cycle by treatment of l-erythr...Continue Reading

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Citations

Aug 15, 2006·Biochimica Et Biophysica Acta·Clara RicciRiccardo Ghidoni
May 23, 2015·Molecules and Cells·Kazuyuki KitataniToshiro Okazaki
Jul 6, 2004·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kazuyasu Nakaya
Dec 12, 2007·Clinical Genetics·A ZayC R Tan-Dy
Nov 28, 2006·Journal of Sports Sciences·Adam R Nicholls, Remco C J Polman
Oct 25, 2006·Experimental Biology and Medicine·Eun Hyun AhnJoseph J Schroeder

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis