Concentration and Composition of Free Ceramides in Human Plasma

Introduction

The biological role of ceramides has been extensively investigated in recent years. Ceramides are the main second messengers in the sphingomyelin transmembrane-signalling pathway. Sphingomyelin is located mostly in the external leaflet of the plasma membrane, and is hydrolysed to phosphorylcholine and ceramide by the enzyme neutral, Mg⁺⁺-dependent sphingomyelinase. This enzyme is also located in the plasma membrane. Certain amounts of ceramides are also formed from sphingomyelin in endo/lysosomes by acidic sphingomyelinase. Both enzymes are activated in a receptor-mediated process [2] [7]. Ceramides are also synthesised de novo from serine and palmitylo-CoA, and generated from other precursors, namely glucosylceramide, galactosylceramide, ceramide-1-phosphate and sphingosine. It is not known, however, to what extent these sources participate in the signal transduction, if at all [2] [7]. A number of stimuli increase ceramide production. These include apoptosis and differentiation inducers, damaging agents and inflammatory cytokines [5].The presence of free ceramides has also been shown in the human plasma [9]. The major ceramide fatty acids were C24 acids, and constituted around 57 % of the total plasma free ceramides. Ceramides containing C22 fatty acids constituted around 24 % of total ceramide fatty acids. Ceramides containing 16, 18, 20 and C23 fatty acids were also present, constituting 5, 4, 4, and 6 % of the total plasma free ceramide fatty acids, respectively [9]. These data were published 30 years ago and have never been verified. Also, a quantitative analysis of saturated and unsaturated ceramide fatty acids was not performed in that study. The aim of the present work was to re-examine the concentration and composition of free ceramide fatty acids in human plasma.

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