Acidic oligosaccharide sugar chain, a marine-derived oligosaccharide, activates human glial cell line-derived neurotrophic factor signaling
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- 作者：XiaoJi Wang ; XueHong Chen ; XinYing Yang ; MeiYu Geng ; LiMei Wang
- 关键词：Glial cell line-derived neurotrophic factor (GDNF) ; Acidic oligosaccharide sugar chain (AOSC) ; Glycosaminoglycans (GAG) ; Heparin sulfate proteoglycan (HSPG) ; Neuroprotection
- 刊名：Neuroscience Letters
- 出版年：2007
- 出版时间：1 May 2007
- 年：2007
- 卷：417
- 期：2
- 页码：176-180
- 全文大小：500 K
文摘
Gial derived neurotrophic factor (GDNF) modulates neuronal cell differentiation during development and protects against neurodegeneration by preventing apoptosis at maturity. GDNF's role in tissue maintenance has generated interest in the therapeutic potential of GDNF in treating neurological disorders such as Parkinson's disease. Heparan sulfate has been shown to be essential for GDNF signaling and altering the levels of heparan sulfate promotes or inhibits GDNF functional activity. To search for other oligosaccharides capable of modulating GDNF activity as potential therapeutic molecules, we investigated the effect of acidic oligosaccharide sugar chain (AOSC) and its sulfated derivative on GDNF induced neurotrophic events by using Western-blotting, immunofluorescence cell staining, and immunoprecipitation techniques in PC12 cells expressing the GDNF receptors GFRα1-Ret. AOSC significantly improved the neurite outgrowth and activated c-Ret phosphorylation in PC12-GFRα1-Ret cells, but its sulfated derivative inhibited GDNF activity. Studies to understand the opposing biological effects of AOSC and its sulfated derivative on GDNF activity demonstrated that reduced GDNF binding to PC12-GFRα1-Ret cell surface in the presence of the sulfated derivative likely suppressed GDNF activity as both AOSC and its sulfated derivatives had similar binding affinities to GDNF. This study illustrates the importance of oligosaccharide structure and charge on influencing GDNF activity and the potential use of oligosaccharides in modulating GDNF activity for therapeutic purposes.