Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Chemical Compound Review:

AG-J-98954 2-aminooctadec-4-ene-1,3-diol

Synonyms: AC1L1AQH, CTK0G8220, IN1085, 6036-85-7, 10140-30-4, ...

Van Koppen, C.J. et al., Okoshi, H. et al., Himmel, H.M. et al.

Van Koppen, Meyer Zu Heringdorf, Zhang, Laser, Jakobs,

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Disease relevance of sphingosine

We therefore investigated the effects of TMS, DMS, and SPN on (a) PA induced by ADP and thrombin; (b) PA induced by melanoma cell line B16/BL6; and (c) experimental lung colonization as well as spontaneous lung metastasis of BL6 cells in syngeneic C57BL/6 mice [1].
The sphingolipids, sphingosylphosphorylcholine (SPPC) and sphingosine-1-phosphate (SPP), induce a rapid and transient rise in intracellular free calcium concentration ([Ca2+]i) in a variety of cell lines via activation of pertussis toxin-sensitive G protein-coupled receptors [2].

High impact information on sphingosine

We recently observed that N,N,N-trimethylsphingosine (TMS) and N,N-dimethylsphingosine (DMS), but not sphingosine (SPN), had an inhibitory effect (via blocking of transmembrane signaling) on the growth of various human tumor cell lines in vitro as well as in vivo in nu/nu mice (K. Endo et al., Cancer Res., 51: 1613-1618, 1991) [1].
The lysosphingolipids sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) reportedly increase free cytosolic Ca2+ concentration ([Ca2+]i) in a variety of cell types, apparently by activating G protein-coupled plasma membrane receptors [3].
We investigated whether these sphingolipids act on different receptors by testing the effect of varying concentrations of SPPC on [Ca2+]i in human leukemia HL-60 cells, which have been found to be nonresponsive to SPP [2].
However, SPPC, but not SPP, stimulated the generation of superoxide anions in dibutyryl cAMP-differentiated HL-60 cells as well as in human neutrophils, suggesting that the SPPC receptor may play a role in the inflammatory defense against invading microorganisms [2].

References

Cell membrane signaling as target in cancer therapy. II: Inhibitory effect of N,N,N-trimethylsphingosine on metastatic potential of murine B16 melanoma cell line through blocking of tumor cell-dependent platelet aggregation. Okoshi, H., Hakomori, S., Nisar, M., Zhou, Q.H., Kimura, S., Tashiro, K., Igarashi, Y. Cancer Res. (1991) [Pubmed]
A distinct G(i) protein-coupled receptor for sphingosylphosphorylcholine in human leukemia HL-60 cells and human neutrophils. Van Koppen, C.J., Meyer Zu Heringdorf, D., Zhang, C., Laser, K.T., Jakobs, K.H. Mol. Pharmacol. (1996) [Pubmed]
Guanine nucleotide-sensitive inhibition of L-type Ca2+ current by lysosphingolipids in RINm5F insulinoma cells. Himmel, H.M., Meyer zu Heringdorf, D., Windorfer, B., van Koppen, C.J., Ravens, U., Jakobs, K.H. Mol. Pharmacol. (1998) [Pubmed]

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