Sphingolipid pathway intermediate
Sphinganine (d18:0) is a precursor of ceramide and sphingosine as well as a substrate of sphingosine kinases, which generate sphinganine-1-phosphate. Sphinganine levels increase significantly in response to certain mycotoxins, including fumonisins,[1,2] as well as in some cancers.[3] Sphinganine can block protein kinase C activation in some cases but not others.[4,5] Sphinganine-1-phosphate can emulate sphingosine-1-phosphate in cell signaling or have opposite intracellular effects.[6,7,8]
参考文献:
1. Pruett, S.T., Bushnev, A., Hagedorn, K., et al. Biodiversity of sphingoid bases ("sphingosines") and related amino alcohols. J. Lipid Res. 49(8), 1621-1639 (2008).
2. Shephard, G.S., van der Westhuizen, L., and Sewram, V. Biomarkers of exposure to fumonisin mycotoxins: A review. Food Addit. Contam. 24(10), 1196-1201 (2007).
3. Yin, J., Miyazaki, K., Shaner, R.L., et al. Altered sphingolipid metabolism induced by tumor hypoxia - new vistas in glycolipid tumor markers. FEBS Lett. 584(9), 1872-1878 (2010).
4. Merrill, A.H., Jr., Sereni, A.M., Stevens, V.L., et al. Inhibition of phorbol ester-dependent differentiation of human promyelocytic leukemic (HL-60) cells by sphinganine and other long-chain bases. J. Biol. Chem. 261(27), 12610-12615 (1986).
5. Merrill, A.H., Jr., Nimkar, S., Menaldino, D., et al. Structural requirements for long-chain (shingoid) base inhibition of protein kinase C in vitro and for the cellular effects of these compounds. Biochemistry 28(8), 3138-3145 (1989).
6. Coste, O., Brenneis, C., Linke, B., et al. Sphingosine 1-phosphate modulates spinal nociceptive processing. J. Biol. Chem. 283(47), 32442-32451 (2008).
7. Bu, S., Yamanaka, M., Pei, H., et al. Dihydrosphingosine 1-phosphate stimulates MMP1 gene expression via activation of ERK1/2-Ets1 pathway in human fibroblasts. FASEB J. 20(1), 184-186 (2006).
8. Bu, S., Kapanadze, B., Hsu, T., et al. Opposite effects of dihydrosphingosine 1-phosphate and sphingosine 1-phosphate on transforming growth factor-β/Smad signaling are mediated through the PTEN/PPM1A-dependent pathway. J. Biol. Chem. 283(28), 19593-19602 (2008).
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