Abstract
Sphingomyelinase catalyzes the hydrolysis of sphingomyelin to generate ceramide, an important molecule involved in the regulation of various cellular responses. In this study, we partially purified the neutral sphingomyelinase2 (nSMase2) and identified the inhibitors, D-lyxophytosphingosine and D-arabino-phytosphingosine, which have an inhibitory effect on nSMase2 in a concentration-dependent manner. A Dixon plot of each phytosphingosines revealed their probable inhibitory pattern, i.e., apparent competitive inhibition. These compounds did not inhibit the Mg(2+)-independent neutral SMase activity, although the known nSMase2 inhibitor, GW4869, showed inhibitory effects on Mg(2+)-independent neutral SMase activity. Further, the two phytosphingosines specifically inhibited the ceramide generation regulated by nSMase2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacology*
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Animals
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Benzylidene Compounds / chemistry
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Benzylidene Compounds / pharmacology*
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Cattle
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Ceramides / metabolism*
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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HEK293 Cells
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Humans
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Magnesium / metabolism
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Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
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Sphingomyelins / metabolism
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Sphingosine / analogs & derivatives*
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Sphingosine / chemistry
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Sphingosine / isolation & purification
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Sphingosine / pharmacology
Substances
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Aniline Compounds
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Benzylidene Compounds
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Ceramides
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D-arabino-phytosphingosine
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Enzyme Inhibitors
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GW 4869
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Sphingomyelins
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lyxo-phytosphingosine
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Sphingomyelin Phosphodiesterase
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Magnesium
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Sphingosine