Identification of three competitive inhibitors for membrane-associated, Mg2+-dependent and neutral 60 kDa sphingomyelinase activity

Methanol extracts of domestic plants of Korea were evaluated as a potential inhibitor of neutral pH optimum and membrane-associated 60 kDa sphingomyelinase (N-SMase) activity. In this study, we partially purified N-SMase from bovine brain membranes using ammonium sulfate. It was purified approximate...

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Bibliographic Details
Published in:Archives of pharmacal research 2005, 28(8), , pp.923-929
Main Authors: Kim, Seok Kyun, Jung, Sang Mi, Ahn, Kyong Hoon, Jeon, Hyung Jun, Lee, Dong Hun, Jung, Kwang Mook, Jung, Sung Yun, Kim, Dae Kyong
Format: Article
Language:English
Subjects:
Abies
Acer
Animals
Binding, Competitive
Brain - drug effects
Brain - enzymology
Cattle
Cell Line, Tumor
Ceramides - biosynthesis
Culture Media, Serum-Free - pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Ginkgo biloba
Humans
Korea
Magnesium
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - isolation & purification
Membrane Proteins - metabolism
Plant Bark
Plant Extracts - pharmacology
Sphingomyelin Phosphodiesterase - antagonists & inhibitors
Sphingomyelin Phosphodiesterase - isolation & purification
Sphingomyelin Phosphodiesterase - metabolism
Sphingomyelins - metabolism
Time Factors
약학
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Summary:Methanol extracts of domestic plants of Korea were evaluated as a potential inhibitor of neutral pH optimum and membrane-associated 60 kDa sphingomyelinase (N-SMase) activity. In this study, we partially purified N-SMase from bovine brain membranes using ammonium sulfate. It was purified approximately 163-fold by the sequential use of DE52, Butyl-Toyopearl, DEAE-Cellulose, and Phenyl-5PW column chromatographies. The purified N-SMase activity was assayed in the presence of the plant extracts of three hundreds species. Based on the in vitro assay, three plant extracts significantly inhibited the N-SMase activity in a time- and concentration-dependent manner. To further examine the inhibitory pattern, a Dixon plot was constructed for each of the plant extracts. The extracts of Abies nephrolepis, Acer tegmentosum, and Ginkgo biloba revealed a competitive inhibition with the inhibition constant (Ki) of 11.9 microg/ mL, 9.4 microg/mL, and 12.9 microg/mL, respectively. These extracts also inhibited in a dose-dependent manner the production of ceramide induced by serum deprivation in human neuroblastoma cell line SH-SY5Y.
ISSN:0253-6269
1976-3786
DOI:10.1007/BF02973878