Because sphingosine (Sph) is actively incorporated into platelets and rapidly converted to sphingosine 1-phosphate (Sph-1-P), which is then released extracellularly, it is important to study the effects of Sph and Sph-1-P on endothelial cells from the viewpoint of platelet-endothelial cell interaction. In this study, we found that Sph, as well as ceramide, induces apoptosis in human umbilical v...

Sphingosine 1-phosphate (Sph-1-P) has been implicated as an intracellular second messenger in many studies. We investigated the metabolism of Sph-1-P and the mechanism by which Sph-1-P induces activation in enucleated and highly differentiated platelets. Platelets lack Sph-1-P lyase activity, possess persistently active sphingosine (Sph) kinase, and abundantly store Sph-1-P. Although exogenous ...

Spectrin is the backbone of the erythroid cytoskeleton; sph/sph mice have severe hereditary spherocytosis (HS) because of a mutation in the murine erythroid alpha-spectrin gene. sph/sph mice have a high incidence of thrombosis and infarction in multiple tissues, suggesting significant vascular dysfunction. In the current study, we provide evidence for both pulmonary and systemic vascular dysfun...

Tetramers of alpha- and beta-spectrin heterodimers, linked by intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either alpha- or beta-spectrin can result in severe hereditary spherocytosis (HS) or hereditary elliptocytosis (HE) in mice and humans. Four mouse mutations, sph, sph(Dem), sph(2BC), and sph(J), affect the erythroid alpha-spect...

Tetramers of αand β-spectrin heterodimers, linked via intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either αor β-spectrin can result in severe hereditary spherocytosis or elliptocytosis (HS/HE) in mice and humans. Four mouse mutations, sph, sph, sph, and sph, affect the erythroid αspectrin gene, Spna1, on Chromosome 1 and cause sever...