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KMID : 0606920110190010134
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Biomolecules & Therapeutics
2011 Volume.19 No. 1 p.134 ~ p.139
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Effects of Synthetic Pseudoceramides on Sphingosine Kinase Activity in F9-12 Cells
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Jin You-Xun
Shin Kyong-Oh
Park Myung-Yong
Lee Shin-Hee
Park Byeong-Deog
Oh Sei-Kwan
Yoo Hwan-Soo
Lee Yong-Moon
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Abstract
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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. Specifi cally, K6PC-5 activated SPHK under the co-treatment with 50 μM dimethylsphingosine (DMS), a SPHK inhibitor. Collectively, we developed a simple SPHK assay system to fi nd 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.
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KEYWORD
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Pseudoceramide, Sphingosine kinase, F9 cells, Assay system
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