Extracellular Export of Sphingosine Kinase-1 Enzyme SPHINGOSINE 1-PHOSPHATE GENERATION AND THE INDUCTION OF ANGIOGENIC VASCULAR MATURATION

摘要: The enzyme sphingosine kinase (SK) catalyzes the formation of 1-phosphate (S1P), a bioactive lipid that acts extracellularly on G protein-coupled receptors S1P1/EDG-1 subfamily. Although S1P is formed in cytosol various cells, release not understood and controversial because this mediator also regarded as second messenger. In report, we describe existence an extracellular S1P-generating system vascular endothelial cells. Endothelial cells SK constitutively form range receptor stimulation. Levels but ATP environment are rate-limiting. Treatment with small interfering RNA for SK-1 transcript specifically inhibited export, SK-1-transfected human embryonic kidney 293 exhibited enhanced SK-1. export constitutive by cytochalasin D treatment at 4 °C brefeldin A or nocodazole, suggesting nonclassical secretory pathway requires actin cytoskeleton dynamics involved. Because regulates angiogenesis maturation, overexpressed using adenoviral vector vivo Matrigel angiogenesis. Overexpression resulted activity induced maturation. These findings suggest made milieu contributes to action system.