文章基本信息

标题：Enhancement of Neurite Outgrowth in PC12 Cells Stimulated with Cyclic AMP and NGF by 6-Acylated Ascorbic Acid 2-O-α-Glucosides (6-Acyl-AA-2G), Novel Lipophilic Ascorbate Derivatives
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作者：Xiaohua Zhou ; Akihiro Tai ; Itaru Yamamoto 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2003
卷号：26
期号：3
页码：341-346
DOI：10.1248/bpb.26.341
出版社：The Pharmaceutical Society of Japan
摘要：It has been shown that ascorbate (AsA) and its stable derivative, ascorbic acid 2- O -α-glucoside (AA-2G), do not elicit neurite outgrowth in PC12 cells. However, these ascorbates are synergistically enhanced by both dibutyryl cyclic AMP (Bt₂cAMP)- and nerve growth factor (NGF)-induced neurite outgrowth in this model. In the present study, the effects of a series of novel lipophilic ascorbate derivatives, 6-acylated ascorbic acid 2- O -α-glucosides (6-Acyl-AA-2G), on neurite outgrowth induced by Bt₂cAMP and NGF were examined in PC12 cells. We found that all the tested acylated ascorbate derivatives enhanced neurite formation induced by both agents in a dose-dependent manner. Of the 6-Acyl-AA-2G derivatives, 6-octanoyl ascorbic acid 2- O -α-glucoside (6-Octa-AA-2G) enhanced the Bt₂cAMP-induced phosphorylated MAPK p44 and p42 expression. A α-glucosidase inhibitor, castanospermine, completely abrogated the promotion of neurite outgrowth and MAPK expression by 6-Octa-AA-2G. Addition of 6-Octa-AA-2G (0.5 m M ) to PC12 cells caused a rapid and significant increase in intracellular AsA content, which reached a maximum and was maintained from 12 to 24 h after the culture. These findings suggest that 6-Acyl-AA-2G is rapidly hydrolyzed to AsA within the cell and enhances neurite differentiation through the interaction with the inducer-activated MAPK pathway.
关键词：ascorbate;lipophilic ascorbate derivative;neurite outgrowth;cAMP;MAP kinase