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Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing mouse brain

Akatsu, Chizuru; Mizumoto, Shuji; Kaneiwa, Tomoyuki; Maccarana, Marco LU ; Malmström, Anders LU ; Yamada, Shuhei and Sugahara, Kazuyuki (2011) In Glycobiology 21(5). p.565-574
Abstract
Chondroitin sulfate (CS) and dermatan sulfate (DS) are expressed in significant amounts in the brain and play important roles in the development of the central nervous system in mammals. CS and DS structures are often found in a single CS/DS hybrid chain. The L-iduronic acid (IdoA)-containing domain, which defines a DS-type domain, appears key to the biological functions of the CS/DS hybrid chain. In this study, to clarify the distribution of the DS-type structure in the brain during development, the expression patterns of DS epimerase 1 (DS-epi1) and DS-epi2, both of which convert D-glucuronic acid into IdoA, were investigated by in situ hybridization. DS-epi2 was ubiquitously expressed in the developing brain after birth, whereas the... (More)
Chondroitin sulfate (CS) and dermatan sulfate (DS) are expressed in significant amounts in the brain and play important roles in the development of the central nervous system in mammals. CS and DS structures are often found in a single CS/DS hybrid chain. The L-iduronic acid (IdoA)-containing domain, which defines a DS-type domain, appears key to the biological functions of the CS/DS hybrid chain. In this study, to clarify the distribution of the DS-type structure in the brain during development, the expression patterns of DS epimerase 1 (DS-epi1) and DS-epi2, both of which convert D-glucuronic acid into IdoA, were investigated by in situ hybridization. DS-epi2 was ubiquitously expressed in the developing brain after birth, whereas the expression of DS-epi1 was faint and obscure at all developmental stages. Quantitative real-time polymerase chain reaction revealed the expression of DS-epi2 to be higher than that of DS-epi1 throughout development, suggesting that DS-epi2 but not DS-epi1 is mostly expressed in the brain and plays key roles in the epimerization of CS/DS during its biosynthesis. Moreover, an analysis of the disaccharides of CS/DS demonstrated significant amounts of IdoA-containing iD units [IdoA(2S)-GalNAc(6S)] and iB units [IdoA(2S)-GalNAc(4S)], where 2S, 4S and 6S stand for 2-O-, 4-O- and 6-O-sulfate, respectively, in every region of the brain examined. The proportion of these units in cerebellar CS/DS was greatly altered during postnatal development. These results suggest that the IdoA-containing structures in the developing brain are mainly produced by the actions of DS-epi2 and play crucial roles in postnatal development. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
* chondroitin sulfate * brain development * dermatan sulfate * dermatan * sulfate epimerase * proteoglycan
in
Glycobiology
volume
21
issue
5
pages
565 - 574
publisher
Oxford University Press
external identifiers
  • wos:000289310500003
  • scopus:79953842941
ISSN
1460-2423
DOI
10.1093/glycob/cwq208
language
English
LU publication?
yes
id
fffa2ff8-a63e-4083-a8e4-8adbf9c39e14 (old id 1965698)
date added to LUP
2011-05-23 14:35:37
date last changed
2017-08-27 04:45:01
@article{fffa2ff8-a63e-4083-a8e4-8adbf9c39e14,
  abstract     = {Chondroitin sulfate (CS) and dermatan sulfate (DS) are expressed in significant amounts in the brain and play important roles in the development of the central nervous system in mammals. CS and DS structures are often found in a single CS/DS hybrid chain. The L-iduronic acid (IdoA)-containing domain, which defines a DS-type domain, appears key to the biological functions of the CS/DS hybrid chain. In this study, to clarify the distribution of the DS-type structure in the brain during development, the expression patterns of DS epimerase 1 (DS-epi1) and DS-epi2, both of which convert D-glucuronic acid into IdoA, were investigated by in situ hybridization. DS-epi2 was ubiquitously expressed in the developing brain after birth, whereas the expression of DS-epi1 was faint and obscure at all developmental stages. Quantitative real-time polymerase chain reaction revealed the expression of DS-epi2 to be higher than that of DS-epi1 throughout development, suggesting that DS-epi2 but not DS-epi1 is mostly expressed in the brain and plays key roles in the epimerization of CS/DS during its biosynthesis. Moreover, an analysis of the disaccharides of CS/DS demonstrated significant amounts of IdoA-containing iD units [IdoA(2S)-GalNAc(6S)] and iB units [IdoA(2S)-GalNAc(4S)], where 2S, 4S and 6S stand for 2-O-, 4-O- and 6-O-sulfate, respectively, in every region of the brain examined. The proportion of these units in cerebellar CS/DS was greatly altered during postnatal development. These results suggest that the IdoA-containing structures in the developing brain are mainly produced by the actions of DS-epi2 and play crucial roles in postnatal development.},
  author       = {Akatsu, Chizuru and Mizumoto, Shuji and Kaneiwa, Tomoyuki and Maccarana, Marco and Malmström, Anders and Yamada, Shuhei and Sugahara, Kazuyuki},
  issn         = {1460-2423},
  keyword      = {* chondroitin sulfate
* brain development
* dermatan sulfate
* dermatan
* sulfate epimerase
* proteoglycan},
  language     = {eng},
  number       = {5},
  pages        = {565--574},
  publisher    = {Oxford University Press},
  series       = {Glycobiology},
  title        = {Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing mouse brain},
  url          = {http://dx.doi.org/10.1093/glycob/cwq208},
  volume       = {21},
  year         = {2011},
}