Absorption and lipoprotein transport of sphingomyelin

From LipidomicsWiki

Sphingomyelin (SM) in mammalian cells is colocalized with cholesterol mainly in the plasma membrane and in lysosomal and Golgi membranes. It interacts strongly with cholesterol, and the regulation of SM and cholesterol metabolism are in part coordinated (Slotte 1999; Redway 2000). In plasma lipoproteins, SM is the second most abundant polar lipid after phosphatidylcholine (PC). The size of the plasma lipoprotein SM pool in humans is 1–1.5 g, of which approximately two-thirds are in apolipoprotein B (apoB)-containing triglyceride (TG)- rich lipoproteins and LDL. The SM content in most extraneural tissues is 1–2 g/kg. Factors regulating plasma SM concentration have received little attention. It was early shown that the level of SM is increased in hypercholesterolemia and that SM-rich lipoproteins accumulate in arteriosclerotic lesions (Portman and Alexander 1970; Portmann and Illingworth 1976, Stein et al. 1969) Plasma SM is thus a risk factor for ischemic heart disease (Jiang et al. 2000), and the apoE-deficient (apoE–/–) mouse, which accumulates SM-rich remnant particles in blood (Jeong et al. 1998), has emerged as an important model for studying the role of SM in atherogenesis. The effects of lipoprotein SM in the arterial wall during atherogenesis may be related both to the modification of lipoproteins and to the generation of sphingolipid messengers (i.e., ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1- phosphate) initiated by SM hydrolysis (Tabas et al. 1993; Gupta and Rudney 1992; Marathe et al. 2000). The role of SM metabolites in cell signaling has been the subject of several recent reviews (Alessenko 2000, Futerman and Hannun 2004; Gulbins and Kolesnick 2003; Hannun et al. 2001; Hannun and Luberto 2004; Marchesini and Hannun 2004). Sphingolipid signals are triggered by numerous stimuli and mediate effects on cell growth and apoptosis and on the activities of inflammatory cells that may be pathogenic as well as protective during the development of the arteriosclerotic lesion (Auge et al. 2000). Recently, myriocin, an inhibitor of SM biosynthesis, was found to selectively decrease plasma SM and to decrease arteriosclerosis in apoE–/– mice (Park et al. 2004; Hojjati et al. 2005), and this finding has been the subject of an editorial comment (Tabas 2004).
Nilsson and Duan (Nilsson and Duan 2006) recently reviewed the absorption and transport of SM and on the biological effects of SM and its metabolites that may be exerted during these processes.