|Research and Education
|Decoding of the biological information in sugar chains（Oka）:|
The function of proteins is regulated in vivo not only by transcriptional control of gene expression but also by post-translational modifications. Glycosylation is one of the major post-translational modifications and a large number of proteins, in fact, undergo this modification. In the post-genomic era, it is very important to decode the biological information encoded in the sugar chains. In our project we focus on structure and function of sugar chains expressed in the nervous system and in development during embryogenesis. To elucidate the roles of the HNK-1 carbohydrate expressed in the nervous system, we have succeeded in generating GlcAT-P gene-deficient mice. The GlcAT-P -/- mice exhibited reduced long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses and defects in spatial memory formation.
The physiological significance of IDO in CNS disorders (Saito):
Indoleamine-2,3-dioxygenase(IDO) production by macrophages and dendritic cells has recently been demonstrated to result in the inhibition of T cell proliferation due to tryptophan depletion by this enzyme. A schematic diagram illustrating the possible role of IDO induction in inflammatory CNS disorders is shown in the figure. IDO plays an important physiological role (both beneficial and detrimental) in the CNS. It has become clear that IDO expression in the CNS is more complicated, to be sure, but regulation of IDO induction must be an ideal therapeutic target to modulate symptoms of various CNS disorders.
Study on acute inflammation associated with transplant rejection（Ikemoto）:
We found a protein that remarkably increased in the serum of the recipients with transplant rejection. This protein is produced by macrophage and/or activated neutrophils in an early stage of acute inflammation, although its functional role remains unclear. We recently found that the protein could indirectly regulate excessive inflammatory responses by binding with inflammatory cytokines nonspecifically. Our goal is to resolve expression mechanism and functional role of the protein in these immunological cells.
||Tagawa, H. et al. (2005) Non-sulfated form of the HNK-1 carbohydrate is expressed in mouse kidney. J. Biol. Chem. 280, 23876-23883.|
||Fujigaki H, Saito K (2006) Nitration and inactivation of indoleamine-2,3-dioxygenase by peroxynitrite.J Immunol. 176:372-379.|
||Shiba, T. et al. (2006) Crystal structure of GlcAT-S, a human glucuronyltransferase, involved in the biosynthesis of the HNK-1 carbohydrate epitope. Proteins 65, 499-508.|
||Kizuka, Y. et al. (2006) Physical and functional association of glucuronyltransferases and sulfotransferase involved in HNK-1 biosynthesis. J. Biol. Chem. 281, 13644-13651.|
||Ikemoto, M. et al. (2007) Intrinsic function of S100A8/A9 complex as an anti-inflammatory protein in liver injury induced by lipopolysaccharide in rats. Clin. Chim. Acta. 376, 197-204.|