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

doi:10.3390/md13127062

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

^1,†,

^2,3,†,

^1,2,†,

^1,2,†,

¹,

¹,

^3,*,

^1,2,*

and

Makoto Kiso

^1,2

Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan

Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan

Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work. ‡ Synthetic studies on sialoglycoconjugates 162. Part 161: Reference 55.

Academic Editor: Antonio Trincone

Mar. Drugs 2015, 13(12), 7250-7274; https://doi.org/10.3390/md13127062

Received: 30 September 2015 / Accepted: 25 November 2015 / Published: 5 December 2015

(This article belongs to the Special Issue Marine Glycoconjugates)

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Abstract

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. View Full-Text

Keywords: ganglioside; starfish; neurite outgrowth; PC12 cell; SH-SY5Y cell; structure-activity relationship; MAPK/ERK signaling

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Yamagishi, M.; Hosoda-Yabe, R.; Tamai, H.; Konishi, M.; Imamura, A.; Ishida, H.; Yabe, T.; Ando, H.; Kiso, M. Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ^‡. Mar. Drugs 2015, 13, 7250-7274. https://doi.org/10.3390/md13127062

AMA Style

Yamagishi M, Hosoda-Yabe R, Tamai H, Konishi M, Imamura A, Ishida H, Yabe T, Ando H, Kiso M. Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ^‡. Marine Drugs. 2015; 13(12):7250-7274. https://doi.org/10.3390/md13127062

Chicago/Turabian Style

Yamagishi, Megumi, Ritsuko Hosoda-Yabe, Hideki Tamai, Miku Konishi, Akihiro Imamura, Hideharu Ishida, Tomio Yabe, Hiromune Ando, and Makoto Kiso. 2015. "Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ^‡" Marine Drugs 13, no. 12: 7250-7274. https://doi.org/10.3390/md13127062

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

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