Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing mouse brain
Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing mouse brain
复制标题
DOI：
10.1093/glycob/cwq208
复制
发表时间：
2011-05-01
期刊：
影响因子：
4.3
通讯作者：
Sugahara, Kazuyuki
中科院分区：
文献类型：
--
作者：
Akatsu, Chizuru;Mizumoto, Shuji;Sugahara, Kazuyuki
硫酸软骨素(CS)和硫酸皮肤素(DS)在脑内大量表达，在哺乳动物中枢神经系统发育中发挥重要作用。CS和DS结构通常存在于单个CS/DS杂化链中。L-艾杜糖酸(IDOA)结构域定义了一个DS类型的结构域，似乎是CS/DS杂交链生物学功能的关键。为了阐明发育过程中DS结构在脑内的分布，本研究利用原位杂交技术研究了DS-EP1和DS-EP2在脑发育过程中的表达模式。DS-EP2在出生后发育的脑组织中普遍表达，而DS-EP1在各个发育阶段的表达都很微弱且不明显。实时定量聚合酶链式反应显示DS-EP2在整个发育过程中的表达高于DS-EP1，表明DS-EP2而不是DS-EP1主要在脑内表达，并在CS/DS生物合成过程中起关键作用。此外，对CS/DS的二糖的分析表明，在所研究的大脑的每个区域中，都有大量含有idoa的ID单位[idoa(2S)-GalNAc(6S)]和IB单位[idoa(2S)-GalNAc(4S)]，其中2S、4S和6S分别代表2-O-、4-O-和6-O-硫酸盐。这些单位在小脑CS/DS中的比例在出生后发育过程中发生了很大的变化。这些结果表明，发育中的大脑中的IDOA结构主要是由DS-EP2的作用产生的，并且在出生后的发育中起着至关重要的作用。
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.