研究者詳細 - 佐藤　ちひろ

Occurrence of free deaminoneuraminic acid (KDN)-containing complex-type N-glycans in human prostate cancers. 査読有り

Yabu M, Korekane H, Takahashi H, Ohigashi H, Ishikawa O, Hatano K, Nonomura N, Sato C, Kitajima K, Miyamoto Y.

Glycobiology 23 巻頁： 634-642 2013年

ポリシアル酸による神経機能の調節. 招待有り査読有り

佐藤ちひろ、北島健

実験医学 31 巻頁： 26--33 2013年

Disialic, oligosialic, and polysialic acids: Distribution, biological functions, and related disease. 招待有り査読有り

Sato C., Kitajima K.

J Biochem (Tokyo). 154 巻頁： 115-136 2013年

Impact of structural aberrancy of polysialic acid and its synthetic enzyme ST8SIA2 in schizophrenia. 査読有り

Sato C, Kitajima K.

Front. Cell. Neurosci. 7 巻 ( 61 ) 頁： 1-11 2013年

Crystal structure of anti-polysialic acid antibody single chain Fv fragment complexed with octasialic acid: insight into the binding preference for polysialic acid. 査読有り

Nagae M, Ikeda A, Hane M, Hanashima S, Kitajima K, Sato C, Yamaguchi Y.

J Biol Chem. 288 巻頁： 33784-96 2013年

ポリシアル酸による神経機能の調節. 招待有り査読有り

佐藤ちひろ, 北島健

実験医学 31 巻頁： 26--33 2013年

Crystal structure of anti-polysialic acid antibody single chain Fv fragment complexed with octasialic acid: insight into the binding preference for polysialic acid. 査読有り

Nagae M, Ikeda A, Hane M, Hanashima S, Kitajima K, Sato C, Yamaguchi Y

J Biol Chem. 288 巻頁： 33784-96 2013年

Impact of structural aberrancy of polysialic acid and its synthetic enzyme ST8SIA2 in schizophrenia. 査読有り

Sato C, Kitajima K

Front. Cell. Neurosci. 7 巻 ( 61 ) 頁： 1-11 2013年

Occurrence of free deaminoneuraminic acid (KDN)-containing complex-type N-glycans in human prostate cancers. 査読有り

Yabu M, Korekane H, Takahashi H, Ohigashi H, Ishikawa O, Hatano K, Nonomura N, Sato C, Kitajima K, Miyamoto Y

Glycobiology 23 巻頁： 634-642 2013年

Pig sperm membrane microdomains contain a highly glycosylated 15-25-kDa wheat germ agglutinin-binding protein. 査読有り

Kasekarn W, Kanazawa T, Hori K, Tsuchiyama T, Lian X, Garénaux E, Kongmanas K, Tanphaichitr N, Yasue H, Sato C, Kitajima K

Biochemical and biophysical research communications 426 巻 ( 3 ) 頁： 356 - 62 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biochemical and Biophysical Research Communications

A highly glycosylated protein, which has unique, novel features in localization, structure, and potential function, is found in pig sperm, and named WGA-gp due to its high binding property with wheat germ agglutinin (WGA). WGA-gp is localized mainly in flagella and enriched in membrane microdomains or lipid rafts. It is not detected by ordinary protein staining methods due to a high content of both N- and O-glycans consisting of neutral monosaccharides. Interestingly, WGA-gp may be involved in intracellular Ca2+ regulation. Treatment of sperm with anti-WGA-gp antibody enhances the amplitude of Ca2+ oscillation without changing the basal intracellular Ca2+ concentrations. All these features of WGA-gp, except for different carbohydrate structures occupying most part of the molecules, are similar to those of flagellasialin in sea urchin sperm, which regulates the intracellular Ca2+ concentration. Presence of carbohydrate-enriched flagellar proteins involved in intracellular Ca2+ regulation may be a common feature among animal sperm. © 2012 Elsevier Inc.

DOI： 10.1016/j.bbrc.2012.08.090

26 ガングリオ系列ガングリオシド糖鎖のコンビナトリアル合成とその機能評価(口頭発表の部)

田中浩士, 西浦祐二, 安田優, 佐藤ちひろ, 北島健, 高橋孝志

天然有機化合物討論会講演要旨集 54 巻 ( 54 ) 頁： 151 - 156 2012年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：天然有機化合物討論会

Gangliosides are a family of glycolipids, which possess sialic acids that play important roles in biological events on cell surfaces. Ganglio-series gangliosides are composed of the tetrasaccharide, (Galβ(1,3)GalNAcβ(1,4)Galβ(1,4)Glc), which bears α(2,8) oligosialic acid units. Glycolipids that vary in number of sialic acids are known as the a-, b-, and c-series of gangliosides. Chemical synthesis of these di-/oligo-sialo-containing glycolipids and their derivatives would facilitate identification of their biological roles. However, the α(2,8) oligosialic acid unit and the compact and rigid 3,4 dibranched galactoside unit are difficult to prepare. Therefore, an effective method for the synthesis of a-, b-, and c-series of gangliosides is still needed. In this report, we describe combinatorial synthesis of ganglio-series ganglioside epitopes varying at the number of the sialic acids. The α(2,3) and α(2,8) sialylations were accomplished by use of 5N,4O-carbonyl and 7,8-O-isopropyliden, and 5N,4O-carbonyl- and 7,8-di-O-chloroacetyl-protected sialyl donors in good yields with excellent a-selectivity, respectively. The two sialyl donors enable synthesis of the di- and tri-sialylgalactosides by simple glycosylation and deprotection. We successfully prepared the ganglioside epitopes via direct construction of a compact, rigid, branched structure. We also reported on a competitive inhibiting activity of the soluble glycolipid library to binding solid-supported GD3 with Siglec-7.

DOI： 10.24496/tennenyuki.54.0_151

CiNii Books

CiNii Research

Metabolism of vertebrate amino sugars with N-glycolyl groups: resistance of α2-8-linked N-glycolylneuraminic acid to enzymatic cleavage. 査読有り

Davies LR, Pearce OM, Tessier MB, Assar S, Smutova V, Pajunen M, Sumida M, Sato C, Kitajima K, Finne J, Gagneux P, Pshezhetsky A, Woods R, Varki A

The Journal of biological chemistry 287 巻 ( 34 ) 頁： 28917 - 28931 2012年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Biological Chemistry

The sialic acid (Sia)N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative N-glycolylneuraminic acid (Neu5Gc) differ by one oxygen atom. CMP-Neu5Gc is synthesized from CMP-Neu5Ac, with Neu5Gc representing a highly variable fraction of total Sias in various tissues and among different species. The exception may be the brain, where Neu5Ac is abundant and Neu5Gc is reported to be rare. Here, we confirm this unusual pattern and its evolutionary conservation in additional samples from various species, concluding that brain Neu5Gc expression has been maintained at extremely low levels over hundreds of millions of years of vertebrate evolution. Most explanations for this pattern do not require maintaining neural Neu5Gc at such low levels. We hypothesized that resistance of α2-8-linked Neu5Gc to vertebrate sialidases is the detrimental effect requiring the relative absence of Neu5Gc from brain. This linkage is prominent in polysialic acid (polySia), a molecule with critical roles in vertebrate neural development.Weshow that Neu5Gc is incorporated into neural polySia and does not cause in vitro toxicity. Synthetic polymers of Neu5Ac and Neu5Gc showed that mammalian and bacterial sialidases are much less able to hydrolyze α2-8-linked Neu5Gc at the nonreducing terminus. Notably, this difference was not seen with acid-catalyzed hydrolysis of polySias. Molecular dynamics modeling indicates that differences in the three-dimensional conformation of terminal saccharides may partly explain reduced enzymatic activity. In keeping with this, polymers of N-propionylneuraminic acid are sensitive to sialidases. Resistance of Neu5Gc-containing polySia to sialidases provides a potential explanation for the rarity of Neu5Gc in the vertebrate brain. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI： 10.1074/jbc.M112.365056

Structural and functional impairments of polySia-NCAM synthesized by a mutated polysialyltransferase of a schizophrenic patient. 査読有り

Hane M, Sumida M, Kitajima K, Sato C.

Pure Appl Chem 84 巻頁： 1895-1906 2012年6月

Structural and functional impairments of polySia-NCAM synthesized by a mutated polysialyltransferase of a schizophrenic patient. 査読有り

Hane M, Sumida M, Kitajima K, Sato C

Pure Appl Chem 84 巻頁： 1895-1906 2012年6月

Sialidase NEU4 Hydrolyzes Polysialic Acids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons 査読有り Open Access

Takahashi, K; Mitoma, J; Hosono, M; Shiozaki, K; Sato, C; Yamaguchi, K; Kitajima, K; Higashi, H; Nitta, K; Shima, H; Miyagi, T

JOURNAL OF BIOLOGICAL CHEMISTRY 287 巻 ( 18 ) 頁： 14816 - 14826 2012年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Biological Chemistry

Modulation of levels of polysialic acid (polySia), a sialic acid polymer, predominantly associated with the neural cell adhesion molecule (NCAM), influences neural functions, including synaptic plasticity, neurite growth, and cell migration. Biosynthesis of polySia depends on two polysialyltransferases ST8SiaII and ST8SiaIV in vertebrate. However, the enzyme involved in degradation of polySia in its physiological turnover remains uncertain. In the present study, we identified and characterized a murine sialidase NEU4 that catalytically degrades polySia. Murine NEU4, dominantly expressed in the brain, was found to efficiently hydrolyze oligoSia and polySia chains as substrates in sialidase in vitro assays, and also NCAM-Fc chimera as well as endogenous NCAM in tissue homogenates of postnatal mouse brain as assessed by immunoblotting with anti-polySia antibodies. Degradation of polySia by NEU4 was also evident in neuroblastoma Neuro2a cells that were co-transfected with Neu4 and ST8SiaIV genes. Furthermore, in mouse embryonic hippocampal primary neurons, the endogenously expressed NEU4 was found to decrease during the neuronal differentiation. Interestingly, GFP- or FLAG-tagged NEU4 was partially co-localized with polySia in neurites and significantly suppressed their outgrowth, whereas silencing of NEU4 showed the acceleration together with an increase in polySia expression. These results suggest that NEU4 is involved in regulation of neuronal function by polySia degradation in mammals. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI： 10.1074/jbc.M111.324186

Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons. 査読有り

Takahashi K, Mitoma J, Hosono M, Shiozaki K, Sato C, Yamaguchi K, Kitajima K, Higashi H, Nitta K, Shima H, Miyagi T.

J Biol Chem. 287 巻頁： 14816-14826 2012年3月

Novel regulation of fibroblast growth factor 2 (FGF2)-mediated cell growth by polysialic acid. 査読有り

Ono S, Hane M, Kitajima K, Sato C

The Journal of biological chemistry 287 巻 ( 6 ) 頁： 3710 - 22 2012年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Biological Chemistry

Polysialic acid (polySia) is a unique polysaccharide that modifies neural cell adhesion molecule (NCAM) spatiotemporally. Recently, we demonstrated that polySia functions as a reservoir for several neurotrophic factors and neurotransmitters. Here, we showed the direct interaction between polySia and fibroblast growth factor-2 (FGF2) by native-PAGE, gel filtration, and surface plasmon resonance. The minimum chain length of polySia required for the interaction with FGF2 was 17. Compared with heparan sulfate, a well known glycosaminoglycan capable of forming a complex with FGF2, polySia formed a larger complex with distinct properties in facilitating oligomerization of FGF2, as well as in binding to FGF receptors. In polySia-NCAM-expressing NIH-3T3 cells, which were established by transfecting cells with either of the plasmids for the expression of the polysialyltransferases ST8SiaII/STX and ST8SiaIV/PST that can polysialylate NCAM, FGF2-stimulated cell growth, but not cell survival, was inhibited. Taken together, these results suggest that polySia-NCAM might be involved in the regulation of FGF2-FGF receptor signaling through the direct binding of FGF2 in a manner distinct from heparan sulfate. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI： 10.1074/jbc.M111.276618