Application Notes:
This product is a high purity, well-defined dihydroceramide that is ideal as a standard and in biological systems.
Dihydroceramide is a critical intermediate in the de novo synthesis of ceramide, leading to many complex sphingolipids. It is
synthesized by the acylation of sphinganine and is subsequently converted to ceramide via the enzyme dihydroceramide
desaturase or into phytosphingosine via the enzyme C4-hydroxylase.1 Inhibition of ceramide synthase by some fungal toxins
(such as fumonisin B1) causes an accumulation of dihydrosphingosine and sphinganine-1-phosphate and a decrease in
dihydroceramide and other dihydrosphingolipids, leading to a number of diseases including oesophageal cancer.2 The
dihydroceramide desaturase inhibitor N-(4-Hydroxyphenyl) retinamide (4-HPR) has been tested as an anti-cancer agent; It
inhibits the dihydroceramide desaturase enzyme in cells resulting in a high concentration of dihydroceramide and dihydrosphingolipids
and this is thought to be the cause of its anti-cancer effects.3 Oxidative stress in cells causes an increase in the
amount of dihydroceramide by potently inhibiting the desaturase enzyme.4 Dihydroceramide inhibits the formation of
channels by ceramides and may thus reduce ceramide induced apoptosis in cells.5 While ceramide is well known for
promoting apoptosis, dihydroceramide has long been considered to be inactive. However, there has recently been evidence
that an accumulation of dihydroceramide can induce cell cycle arrest.6
References:
1. Y. Mizutani, A. Kihara, and Y. Igarashi “Identifcation of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte
differentiation” FEBS Letters, vol. 563 pp. 93-97, 2004
2. J. Soriano et al. “Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1” Progress in Lipid Research, Vol. 44 pp.
345-356, 2005
3. W. Zheng “Fenretinide increases dihydroceramide and dihydrosphingolipids due to inhibition of dihydroceramide desaturase” Georgia Institute of
Technology, 2006
4. J. Idkowiak-Baldys et al. “Dihydroceramide Desaturase Activity is Modulated by Oxidative Stress” Biochem. J., Vol. 427(2) pp. 265-274, 2010
5. J. Stiban et al. “Dihydroceramide hinders ceramide channel formation: Implications on apoptosis” Apoptosis, Vol. 11(5) pp. 773-780, 2006
6. J. Kraveka et al. “Involvement Of The Dihydroceramide Desaturase In Cell Cycle Progression In Human Neuroblastoma Cells” Journal of Biological
Chemistry., Vol. 282(23) pp. 16718-16728, 2007