Identification and Evaluation of Neutral Sphingomyelinase 2 Inhibitors
Identification and Evaluation of Neutral Sphingomyelinase 2 Inhibitors
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DOI：
10.1007/s12272-011-0208-y
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发表时间：
2011-02-01
影响因子：
6.7
通讯作者：
Kim, Dae Kyong
中科院分区：
文献类型：
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作者：
Lee, Dong Hun;Kim, Sung Hyun;Kim, Dae Kyong
鞘磷脂酶催化鞘磷脂水解生成神经酰胺，神经酰胺是调节各种细胞反应的重要分子。本研究部分纯化了中性鞘磷脂酶2 (nSMase2)，并鉴定出对nSMase2具有浓度依赖性抑制作用的抑制剂d -lyxo-phytosphingosin和d -arabino-phytosphingosin。每种植物鞘烷素的Dixon图揭示了它们可能的抑制模式，即明显的竞争性抑制。尽管已知的nSMase2抑制剂GW4869对Mg2+非依赖性中性SMase活性有抑制作用，但这些化合物对Mg2+非依赖性中性SMase活性没有抑制作用。此外，两种植物鞘苷特异性抑制nSMase2调控的神经酰胺生成。
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-lyxo-phytosphingosine 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 Mg2+-independent neutral SMase activity, although the known nSMase2 inhibitor, GW4869, showed inhibitory effects on Mg2+-independent neutral SMase activity. Further, the two phytosphingosines specifically inhibited the ceramide generation regulated by nSMase2.