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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
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 | Cartilage | 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) |
URI: | http://hdl.handle.net/2115/45301 |
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)
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Submitter: 菅原 一幸
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