文章基本信息

标题：Strong Inhibition of Secretory Sphingomyelinase by Catechins, Particularly by (−)-Epicatechin 3-O-Gallate and (−)-3′-O-Methylepigallocatechin 3-O-Gallate
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作者：Keiko KOBAYASHI ; Yuki ISHIZAKI ; Shosuke KOJO 等
期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2016
卷号：62
期号：2
页码：123-129
DOI：10.3177/jnsv.62.123
出版社：Center for Academic Publications Japan
摘要：Sphingomyelinases (SMases) are key enzymes involved in many diseases which are caused by oxidative stress, such as atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease, and Alzheimer’s disease. SMases hydrolyze sphingomyelin to generate ceramide, a well-known pro-apoptotic lipid. SMases are classified into five types based on pH optimum, subcellular localization, and cation dependence. Previously, we demonstrated that elevation of secretory sphingomyelinase (sSMase) activity increased the plasma ceramide concentration under oxidative stress induced by diabetes and atherosclerosis in murine models. These results suggest that sSMase inhibitors can prevent the progress of these diseases. The present study demonstrated that sSMase activity was activated by oxidation and inhibited by reduction. Furthermore, we examined whether catechins inhibited the sSMase activity in a physiological plasma concentration. Among catechins, (−)-epicatechin 3- O -gallate (ECg) exhibited strong inhibitory effect on sSMase (IC₅₀=25.7 μ M ). This effect was attenuated by methylation at the 3″- or 4″-position. On the other hand, (−)-epigallocatechin 3- O -gallate (EGCg) and (−)-catechin 3- O -gallate (Cg) exhibited weaker inhibitory activity than ECg, and (−)-epicatechin and (−)-epigallocatechin did not affect sSMase activity. Additionally, one synthetic catechin, (−)-3′- O -methylepigallocatechin 3- O -gallate (EGCg-3′-O-Me), showed the strongest inhibitory effect (IC₅₀=1.7 μ M ) on sSMase. This phenomenon was not observed for (−)-4′- O -methylepigallocatechin 3- O -gallate. These results suggest that the reduction potential, the presence of the galloyl residue at the C-3 position, and the steric requirement to interact with sSMase protein are important for effective inhibition of sSMase.
关键词：sphingomyelinase;redox;catechin;antioxidant