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Demonstration of the hepatocyte growth factor signaling pathway in the in vitro neuritogenic activity of chondroitin sulfate from ray fish cartilage

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Title: Demonstration of the hepatocyte growth factor signaling pathway in the in vitro neuritogenic activity of chondroitin sulfate from ray fish cartilage
Authors: Hashiguchi, Taishi Browse this author
Kobayashi, Takanari Browse this author
Fongmoon, Duriya Browse this author
Shetty, Ajaya Kumar Browse this author
Mizumoto, Shuji Browse this author
Miyamoto, Nobuyuki Browse this author
Nakamura, Toshikazu Browse this author
Yamada, Shuhei Browse this author
Sugahara, Kazuyuki Browse this author
Keywords: Chondroitin sulfate
Neurite outgrowth-promoting activity
Hepatocyte growth factor
c-Met receptor
Issue Date: Apr-2011
Publisher: Elsevier B.V.
Journal Title: Biochimica et Biophysica Acta (BBA) : General Subjects
Volume: 1810
Issue: 4
Start Page: 406
End Page: 413
Publisher DOI: 10.1016/j.bbagen.2011.01.001
PMID: 21223992
Abstract: Chondroitin sulfate (CS) was isolated from ray fish cartilage, an industrial waste, after protease digestion, and its structure and neurite outgrowth-promoting (NOP) activity were analyzed to investigate a potential application to nerve regeneration. A disaccharide analysis using chondroitinase ABC revealed that the major unit in the CS preparation was GlcUA-GalNAc(6-O-sulfate) (63%), where GlcUA and GalNAc represent D-glucuronic acid and N-acetyl-D-galactosamine, respectively. Small proportions of other disaccharide units, GlcUA-GalNAc(4-O-sulfate) (25%), GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate) (7%), and GlcUA-GalNAc (5%), were also detected. The average molecular mass of CS was estimated to be 142 kDa by gel-filtration chromatography. The prepration showed NOP activity in vitro, which was eliminated by digestion with chondroitinase ABC, suggesting that a polymeric structure is required for the activity. Antibodies against hepatocyte growth factor (HGF) and its receptor c-Met suppressed the NOP activity, suggesting the involvement of the HGF signaling pathway in the in vitro NOP activity of the CS preparation. Since the specific binding of HGF to the CS preparation was also demonstrated by surface plasmon resonance spectroscopy, the CS chains were fractionated using an HGF-immobilized column into unbound and bound fractions accounting for 44 and 56% of the total yield, respectively. The latter contained a higher proportion of the GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate) unit, and showed greater NOP activity than the former, indicating that the HGF-binding domain contains GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate) and is involved in the NOP activity. CS from ray cartilage may have potential pharmaceutical applications.
Type: article (author version)
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 菅原 一幸

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