• Proceedings of the PSK Conference
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• 2003.10b
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• pp.76.2-76.2
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• 2003

Although sphingosine-1-phosphate (S1P) is a well-known mitogen, our results show that S1P potently inhibits keratinocyte proliferation, and that this leads the inhibition of DNA synthesis. Interestingly, the prolonged activation of extracellular signal-regulated protein kinase (ERK) and the transient inactivation of Akt/protein kinase B (PKB) were also oberved in concert with the inhibition of keratinocyte proliferation by S1P. To further verify the anti-proliferative action of S1P, we examined changes in cell cycle related proteins. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.77.3-78
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• 2003

We previously shown that sphingosylphosphorylcholine, a lysophosphatidic acid, produced contraction in isolated single cells of cat ilium. We investigated the mechanism of sphingosine-1-phosphate (S1P)-induced contraction of circular smooth muscle cells in cat esophagus. S1P produced esophageal contraction in a dose dependent manner. The maximal contraction (l0$\^$-7/ M) induced at 1min. Pertusis toxin (PTX) inhibited contraction induced by S1P, suggesting that the contraction is mediated to a PTX-sensitive G-protein. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.95.2-96
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• 2003

Ultraviolet B (UVB) is known to induce apoptosis in human melanocytes. Here we show the cytoprotective effect of sphingosine-1-phosphate (S1P) against UVB-induced apoptosis. We also show that UVB-induced apoptosis of melanocytes is mediated by caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage, and that S1P prevents apoptosis by inhibiting this apoptotic pathway. We further investigated three major subfamilies of mitogen-activated protein (MAP) kinases and the Akt pathway after UVB irradiation. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.271.1-271.1
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• 2002

Sphingolipids have been emerged as bioactive lipid modulators that mediate a variety of cell functions. However. the effects of sphingolipids on the cell growth and survival of melanocytes are not yet known. In the present study, we investigated the actions of sphingolipids in Mel-Ab melanocytes. We observed the cytoprotective effect of sphingosine-1-phosphate (SPP) on UVB-induced cell death. (omitted)

• Biomolecules & Therapeutics
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• v.25 no.1
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• pp.1-3
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• 2017

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.99.1-99.1
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• 2002

• BMB Reports
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• v.42 no.10
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• pp.685-690
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• 2009

Angiogenesis is essential for tumor growth and vascular endothelial cell growth factor (VEGF) plays a key role in this process. Conversely, sphingosine 1-phosphate (S1P) is a biologically active sphingolipid known to play a key role in cancer progression by regulating endothelial cell proliferation and migration. In this study, the authors found that S1P increases the level of VEGF mRNA in human umbilical vein endothelial cells (HUVECs) and immortalized HUVECs (iHUVECs). Additionally, S1P was found to increase VEGF promoter activity in MS-1 mouse pancreatic islet endothelial cells. Furthermore, a pharmacological inhibitory study revealed that $G_{\alpha i/o}$-mediated phospholipase C, Akt, Erk, and p38 MAPK signaling are involved in this S1P-induced expression of VEGF. A component of AP1 transcription factor is important for S1P-induced VEGF expression. Taken together, these findings suggest that S1P enhances endothelial cell proliferation and migrat ion by upregulating the expression of VEGF mRNA.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.271.3-272
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• 2002

This study shows that sphingosine-1-phosphate (SPP) significantly inhibits melanin synthesis in a concentration-dependent manner, and that the activity of tyrosinase was also reduced in SPP-treated cells. In contrast. a specific extracellular signal-regulated protein kinase (ERK) pathway inhibitor, PD98059 increased tyrosinase activity and melanin production, and PD98059 restored the reduced tyrosinase activity and pigmentation induced by SPP. (omitted)

• BMB Reports
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• v.53 no.1
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• pp.28-34
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• 2020

Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes that function as signaling molecules for regulating a diverse range of cellular processes, including cell proliferation, growth, survival, immune-cell trafficking, vascular and epithelial integrity, and inflammation. Recently, several studies have highlighted the pivotal role of sphingolipids in neuroinflammatory regulation. Sphingolipids have multiple functions, including induction of the expression of various inflammatory mediators and regulation of neuroinflammation by directly effecting the cells of the central nervous system. Accumulating evidence points to sphingolipid engagement in neuroinflammatory disorders, including Alzheimer's and Parkinson's diseases. Abnormal sphingolipid alterations, which involves an increase in ceramide and a decrease in sphingosine kinase, are observed during neuroinflammatory disease. These trends are observed early during disease development, and thus highlight the potential of sphingolipids as a new therapeutic and diagnostic target for neuroinflammatory diseases.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.134-139
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• 2011

Sphingosine kinase (SPHK) has a central role to control cell death and cell proliferation, which is suggested as a sphingolipid rheostat by regulating the levels between ceramide and sphingosine 1-phosphate (S1P). Therefore, physiological regulators of SPHK will be a good candidate to develop a new targeted drug. For this purpose, a series of synthetic pseudoceramides were tested by SPHK assay either cell-based or cell-free system. K10PC-5 strongly inhibited SPHK, while K6PC-5 activated SPHK in cell-free system. Specifically, K6PC-5 activated SPHK under the co-treatment with $50\;{\mu}M$ dimethylsphingosine (DMS), a SPHK inhibitor. Collectively, we developed a simple SPHK assay system to find SPHK regulatory pseudoceramide compounds, K10PC-5 and K6PC-5 which may be useful to cancer treatment or immune regulation like FTY720, a synthetic sphingolipid mimetic compound.