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The ganglioside patterns have been shown to dramatically change during cell proliferation and differentiation and in certain cell-cycle phases, brain development, and cancer malignancy. To investigate the significance of the ganglioside GM3 in cancer malignancy, we established GM3-reconstituted cells by transfecting the cDNA of GM3 synthase into a(More)
The lysophospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are now recognized as important extracellular signaling molecules. These lipid mediators are pleiotropic; among the most common cellular responses are mitogenesis, cell survival (anti-apoptosis), inhibition of adenylyl cyclase and calcium mobilization. Physiologic events(More)
Platelets are known to store a large amount of the bioactive lipid molecule sphingosine 1-phosphate (S1P) and to release it into the plasma in a stimuli-dependent manner. Erythrocytes can also release S1P, independently from any stimuli. We measured the S1P and sphingosine (Sph) levels in erythrocytes by HPLC and found that the contribution of erythrocyte(More)
Sphingosine 1-phosphate (S1P) is accumulated in platelets and released on stimulation by thrombin or Ca(2+). Thrombin-stimulated S1P release was inhibited by staurosporin, whereas Ca(2+)-stimulated release was not. When the platelet plasma membrane was permeabilized with streptolysin O (SLO), S1P leaked out with cytosol markers, whereas granular markers(More)
Elevated amyloid-β peptide (Aβ) in brain contributes to Alzheimer's disease (AD) pathogenesis. We demonstrated the presence of exosome-associated Aβ in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. The levels of exosome-associated Aβ notably decreased in the CSF of aging animals. We also determined that neuronal exosomes, but(More)
The serum-borne lysophospholipid mediators sphingosine 1-phosphate (Sph-1-P) and lysophosphatidic acid (LPA) have been shown to be released from activated platelets and to act on endothelial cells. In this study, we employed the repeated lipid extraction (under alkaline and acidic conditions), capable of detecting Sph-1-P, LPA, and possibly structurally(More)
Activation of the PDGF receptor on human arterial smooth muscle cells (SMC) induces migration and proliferation via separable signal transduction pathways. Sphingosine-1-phosphate (Sph-1-P) can be formed following PDGF receptor activation and therefore may be implicated in PDGF-receptor signal transduction. Here we show that Sph-1-P does not significantly(More)
The novel immunomodulator FTY720 causes lymphocytes from peripheral blood to accumulate in lymphoid tissues. In vivo, FTY720 is phosphorylated to FTY720-P, which binds to the sphingosine 1-phosphate receptor S1P(1). So far, it has been unclear where FTY720-P is produced. We demonstrate that platelets efficiently convert FTY720 to FTY720-P and release it(More)
The present studies were undertaken to characterize the potential role of sphingosine in the regulation of apoptosis in III-t.O promyelocytic leukemia cells. A 6-h exposure of HL-60 cells to sphingosine or its meth ylated derivative, /VVV-dimethylsphingosine, caused internucleosomal DNA fragmentation and stereotypical morphological changes character istic(More)
Sphingolipid breakdown products, including ceramide and sphingosine, regulate cell growth, cell differentiation, and apoptosis. We examined the effect of various agents, including sphingolipids, on apoptosis induction in human epidermoid carcinoma KB-3-1 and its multidrug-resistant (MDR) subclone KB-C2 cells which express P-glycoprotein. Adriamycin (ADM)(More)