HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 24, 23184-23193, June 17, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/24/23184    most recent M503036200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bao, X. Articles by Sugahara, K. Search for Related Content PubMed PubMed Citation Articles by Bao, X. Articles by Sugahara, K. Social Bookmarking                      What's this?

A Functional Dermatan Sulfate Epitope Containing Iduronate(2-O-sulfate)1–3GalNAc(6-O-sulfate) Disaccharide in the Mouse Brain

DEMONSTRATION USING A NOVEL MONOCLONAL ANTIBODY RAISED AGAINST DERMATAN SULFATE OF ASCIDIAN ASCIDIA NIGRA^*

Xingfeng Bao, Mauro S. G. Pavão¶||, Joana Cabral dos Santos¶, and Kazuyuki Sugahara, Supported by CREST, JST**

From the Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan and the ^¶Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica, Programa de Glicobiologia, Universidade Federal do Rio de Janeiro, Caixa Postal 68041, Rio de Janeiro, RJ 21941-590, Brazil

Oversulfated chondroitin sulfate (CS), dermatan sulfate (DS), and CS/DS hybrid structures bind growth factors, promote the neurite outgrowth of hippocampal neurons in vitro, and have been implicated in the development of the brain. To investigate the expression of functional oversulfated DS structures in the brain, a novel monoclonal antibody (mAb), 2A12, was generated against DS (An-DS) from ascidian Ascidia nigra, which contains a unique iD disaccharide unit, iduronic acid (2-O-sulfate)13GalNAc(6-O-sulfate), as a predominant disaccharide. mAb 2A12 specifically reacted with the immunogen, and recognized iD-enriched decasaccharides as minimal structures. The 2A12 epitope was specifically observed in the hippocampus and cerebellum of the mouse brain on postnatal day 7, and the expression in the cerebellum disappeared in the adult brain, suggesting a spatiotemporally regulated expression of this epitope. Embryonic hippocampal neurons were immunopositive for 2A12, and the addition of the antibody to the culture medium significantly reduced the neurite growth of hippocampal neurons. In addition, two minimum 2A12-reactive decasaccharide sequences with multiple consecutive iD units were isolated from the An-DS chains, which exhibited stronger inhibitory activity against the binding of various growth factors and neurotrophic factors to immobilized embryonic pig brain CS/DS chains (E-CS/DS) than the intact E-CS/DS, suggesting that the 2A12 epitope at the neuronal surface acts as a receptor or co-receptor for these molecules. Thus, we have selected a unique antibody that recognizes iD-enriched oversulfated DS structures, which are implicated in the development of the hippocampus and cerebellum in the central nervous system. The antibody will also be applicable for investigating structural alterations in CS/DS in aging and pathological conditions.

Received for publication, March 18, 2005

^* This work was supported in part by HAITEKU (2004–2008) from the Japan Private School Promotion Foundation, and Grants-in-aid for Exploratory Research 15659021 and Scientific Research-B 16390026 from MEXT. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported in part by postdoctoral fellowships from JSPS and HAITEKU.

^|| Supported in part by the National Institutes of Health, Fogarty International Center Grant R03 TW05775, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.

^** To whom correspondence should be addressed: Dept. of Biochemistry, Kobe Pharmaceutical University, 4-19-1, Motoyama-kita-machi, Higashinada-ku, Kobe 658-8558, Japan. Tel.: 81-78-441-7570; Fax: 81-78-441-7569; E-mail: k-sugar{at}kobepharma-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Ueyama, H. Takemae, Y. Ohmae, H. Yoshida, H. Toyoda, R. Ueda, and S. Nishihara Functional Analysis of Proteoglycan Galactosyltransferase II RNA Interference Mutant Flies J. Biol. Chem., March 7, 2008; 283(10): 6076 - 6084. [Abstract] [Full Text] [PDF]

				K. Akita, A. von Holst, Y. Furukawa, T. Mikami, K. Sugahara, and A. Faissner Expression of Multiple Chondroitin/Dermatan Sulfotransferases in the Neurogenic Regions of the Embryonic and Adult Central Nervous System Implies That Complex Chondroitin Sulfates Have a Role in Neural Stem Cell Maintenance Stem Cells, March 1, 2008; 26(3): 798 - 809. [Abstract] [Full Text] [PDF]

				K. R. Catlow, J. A. Deakin, Z. Wei, M. Delehedde, D. G. Fernig, E. Gherardi, J. T. Gallagher, M. S. G. Pavao, and M. Lyon Interactions of Hepatocyte Growth Factor/Scatter Factor with Various Glycosaminoglycans Reveal an Important Interplay between the Presence of Iduronate and Sulfate Density J. Biol. Chem., February 29, 2008; 283(9): 5235 - 5248. [Abstract] [Full Text] [PDF]

				P. Pothacharoen, K. Kalayanamitra, S. S. Deepa, S. Fukui, T. Hattori, N. Fukushima, T. Hardingham, P. Kongtawelert, and K. Sugahara Two Related but Distinct Chondroitin Sulfate Mimetope Octasaccharide Sequences Recognized by Monoclonal Antibody WF6 J. Biol. Chem., November 30, 2007; 282(48): 35232 - 35246. [Abstract] [Full Text] [PDF]

				G. B. ten Dam, E. M.A. van de Westerlo, A. Purushothaman, R. V. Stan, J. Bulten, F. C.G.J. Sweep, L. F. Massuger, K. Sugahara, and T. H. van Kuppevelt Antibody GD3G7 Selected against Embryonic Glycosaminoglycans Defines Chondroitin Sulfate-E Domains Highly Up-Regulated in Ovarian Cancer and Involved in Vascular Endothelial Growth Factor Binding Am. J. Pathol., October 1, 2007; 171(4): 1324 - 1333. [Abstract] [Full Text] [PDF]

				A. Purushothaman, J. Fukuda, S. Mizumoto, G. B. ten Dam, T. H. van Kuppevelt, H. Kitagawa, T. Mikami, and K. Sugahara Functions of Chondroitin Sulfate/Dermatan Sulfate Chains in Brain Development: CRITICAL ROLES OF E AND iE DISACCHARIDE UNITS RECOGNIZED BY A SINGLE CHAIN ANTIBODY GD3G7 J. Biol. Chem., July 6, 2007; 282(27): 19442 - 19452. [Abstract] [Full Text] [PDF]

				S. S Deepa, S. Yamada, S. Fukui, and K. Sugahara Structural determination of novel sulfated octasaccharides isolated from chondroitin sulfate of shark cartilage and their application for characterizing monoclonal antibody epitopes Glycobiology, June 1, 2007; 17(6): 631 - 645. [Abstract] [Full Text] [PDF]

				D. Xu, D. Song, L. C. Pedersen, and J. Liu Mutational Study of Heparan Sulfate 2-O-Sulfotransferase and Chondroitin Sulfate 2-O-Sulfotransferase J. Biol. Chem., March 16, 2007; 282(11): 8356 - 8367. [Abstract] [Full Text] [PDF]

				M. J. C. Miller, C. E. Costello, A. Malmstrom, and J. Zaia A tandem mass spectrometric approach to determination of chondroitin/dermatan sulfate oligosaccharide glycoforms Glycobiology, June 1, 2006; 16(6): 502 - 513. [Abstract] [Full Text] [PDF]

				X. Bao, T. Muramatsu, and K. Sugahara Demonstration of the Pleiotrophin-binding Oligosaccharide Sequences Isolated from Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains of Embryonic Pig Brains J. Biol. Chem., October 21, 2005; 280(42): 35318 - 35328. [Abstract] [Full Text] [PDF]