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Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡

LLG-3 is a ganglioside isolated from the starfish Linchia laevigata. To clarify the structure-activity relationship of the glycan of LLG-3 toward rat pheochromocytoma PC12 cells in the presence of nerve growth factor, a series of mono- to tetrasaccharide glycan derivatives were chemically synthesize...

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Autores principales: Yamagishi, Megumi, Hosoda-Yabe, Ritsuko, Tamai, Hideki, Konishi, Miku, Imamura, Akihiro, Ishida, Hideharu, Yabe, Tomio, Ando, Hiromune, Kiso, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699235/
https://www.ncbi.nlm.nih.gov/pubmed/26690179
http://dx.doi.org/10.3390/md13127062
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author Yamagishi, Megumi
Hosoda-Yabe, Ritsuko
Tamai, Hideki
Konishi, Miku
Imamura, Akihiro
Ishida, Hideharu
Yabe, Tomio
Ando, Hiromune
Kiso, Makoto
author_facet Yamagishi, Megumi
Hosoda-Yabe, Ritsuko
Tamai, Hideki
Konishi, Miku
Imamura, Akihiro
Ishida, Hideharu
Yabe, Tomio
Ando, Hiromune
Kiso, Makoto
author_sort Yamagishi, Megumi
collection PubMed
description LLG-3 is a ganglioside isolated from the starfish Linchia laevigata. To clarify the structure-activity relationship of the glycan of LLG-3 toward rat pheochromocytoma PC12 cells in the presence of nerve growth factor, a series of mono- to tetrasaccharide glycan derivatives were chemically synthesized and evaluated in vitro. The methyl group at C8 of the terminal sialic acid residue was crucial for neuritogenic activity, and the terminal trisaccharide moiety was the minimum active motif. Furthermore, the trisaccharide also stimulated neuritogenesis in human neuroblastoma SH-SY5Y cells via mitogen-activated protein kinase (MAPK) signaling. Phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was rapidly induced by adding 1 or 10 nM of the trisaccharide. The ratio of phosphorylated ERK to ERK reached a maximum 5 min after stimulation, and then decreased gradually. However, the trisaccharide did not induce significant Akt phosphorylation. These effects were abolished by pretreatment with the MAPK inhibitor U0126, which inhibits enzymes MEK1 and MEK2. In addition, U0126 inhibited the phosphorylation of ERK 1/2 in response to the trisaccharide dose-dependently. Therefore, we concluded that the trisaccharide promotes neurite extension in SH-SY5Y cells via MAPK/ERK signaling, not Akt signaling.
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spelling pubmed-46992352016-01-21 Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡ Yamagishi, Megumi Hosoda-Yabe, Ritsuko Tamai, Hideki Konishi, Miku Imamura, Akihiro Ishida, Hideharu Yabe, Tomio Ando, Hiromune Kiso, Makoto Mar Drugs Article LLG-3 is a ganglioside isolated from the starfish Linchia laevigata. To clarify the structure-activity relationship of the glycan of LLG-3 toward rat pheochromocytoma PC12 cells in the presence of nerve growth factor, a series of mono- to tetrasaccharide glycan derivatives were chemically synthesized and evaluated in vitro. The methyl group at C8 of the terminal sialic acid residue was crucial for neuritogenic activity, and the terminal trisaccharide moiety was the minimum active motif. Furthermore, the trisaccharide also stimulated neuritogenesis in human neuroblastoma SH-SY5Y cells via mitogen-activated protein kinase (MAPK) signaling. Phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was rapidly induced by adding 1 or 10 nM of the trisaccharide. The ratio of phosphorylated ERK to ERK reached a maximum 5 min after stimulation, and then decreased gradually. However, the trisaccharide did not induce significant Akt phosphorylation. These effects were abolished by pretreatment with the MAPK inhibitor U0126, which inhibits enzymes MEK1 and MEK2. In addition, U0126 inhibited the phosphorylation of ERK 1/2 in response to the trisaccharide dose-dependently. Therefore, we concluded that the trisaccharide promotes neurite extension in SH-SY5Y cells via MAPK/ERK signaling, not Akt signaling. MDPI 2015-12-05 /pmc/articles/PMC4699235/ /pubmed/26690179 http://dx.doi.org/10.3390/md13127062 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yamagishi, Megumi
Hosoda-Yabe, Ritsuko
Tamai, Hideki
Konishi, Miku
Imamura, Akihiro
Ishida, Hideharu
Yabe, Tomio
Ando, Hiromune
Kiso, Makoto
Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡
title Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡
title_full Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡
title_fullStr Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡
title_full_unstemmed Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡
title_short Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡
title_sort structure-activity relationship study of the neuritogenic potential of the glycan of starfish ganglioside llg-3 ‡
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699235/
https://www.ncbi.nlm.nih.gov/pubmed/26690179
http://dx.doi.org/10.3390/md13127062
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