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Identification and evaluation of neutral sphingomyelinase 2 inhibitors

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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 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.

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Authors and Affiliations

  1. Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea

    Dong Hun Lee, Sung Hyun Kim, Kyong Hoon Ahn, Seok Kyun Kim, Jong Min Choi, Jung Eun Ji, Jong Hoon Won, Yang Hui Park & Dae Kyong Kim

  2. College of Pharmacy, Seoul National University, Seoul, 151-742, Korea

    Chaemin Lim & Sanghee Kim

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  1. Dong Hun Lee
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Correspondence to Dae Kyong Kim.

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Lee, D.H., Kim, S.H., Ahn, K.H. et al. Identification and evaluation of neutral sphingomyelinase 2 inhibitors. Arch. Pharm. Res. 34, 229–236 (2011). https://doi.org/10.1007/s12272-011-0208-y

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