RRC ID 67309
Author Yamagishi M, Hosoda-Yabe R, Tamai H, Konishi M, Imamura A, Ishida H, Yabe T, Ando H, Kiso M.
Title Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 (‡).
Journal Mar Drugs
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.
Volume 13(12)
Pages 7250-74
Published 2015-12-5
DOI 10.3390/md13127062
PII md13127062
PMID 26690179
PMC PMC4699235
MeSH Animals Butadienes / administration & dosage Butadienes / pharmacology Dose-Response Relationship, Drug Gangliosides / chemistry Gangliosides / isolation & purification Gangliosides / pharmacology* Humans Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Nerve Growth Factor / metabolism Neurites / drug effects* Neurites / metabolism Neuroblastoma / metabolism Nitriles / administration & dosage Nitriles / pharmacology PC12 Cells Phosphorylation / drug effects Polysaccharides / chemistry Polysaccharides / isolation & purification Polysaccharides / pharmacology* Rats Signal Transduction / drug effects Starfish / metabolism* Structure-Activity Relationship
IF 4.073
Resource
Human and Animal Cells PC-12(RCB0009)