Quantification of sphingosine derivatives in human platelets: inducible formation of free sphingosine

Journal of Biochemistry
N HisanoY Ozaki

Abstract

To elucidate the physiologic role of sphingolipid-derived products as signaling molecules, we analyzed the levels of endogenous sphingosine (Sph) derivatives in human platelets. When the platelets were stimulated with thrombin or 12-O-tetradecanoylphorbol 13-acetate, neither ceramide formation nor sphingomyelin hydrolysis was observed, which suggests that the sphingomyelin cycle may not be an essential part of the signaling pathway under these conditions. In contrast, Sph was found to increase in platelets upon stimulation. The level of Sph 1-phosphate, which is formed from Sph by the action of Sph kinase, was not affected under our conditions. Although it has been established that Sph inhibits protein kinase C, which regulates the functional responses of the platelets, Sph levels which exert an inhibitory effect on protein kinase C cannot be attained under physiological conditions (without exogenous Sph). Considering the stimulation of the synthesis of Sph by the physiological agonist thrombin, we speculate that Sph is a signaling molecule of physiological importance in platelets, but protein kinase C may not be its target.

Citations

Apr 23, 1999·Thrombosis Research·C G Simon, A R Gear
Jun 1, 2000·Biochimica Et Biophysica Acta·A HuwilerK Sandhoff
Dec 3, 1999·British Journal of Haematology·L YangY Ozaki
Jan 9, 2003·Annual Review of Physiology·Martha M Monick, Gary W Hunninghake
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martha M MonickGary W Hunninghake
Jul 13, 2005·Biochemical and Biophysical Research Communications·Wojciech KalasJanusz Rak

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