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Naoyuki Taniguchi

Publications and source records attributed to Naoyuki Taniguchi.

114 records · Page 7Linked to original sources
PubMed2002

UDP-GlcNAc concentration is an important factor in the biosynthesis of beta1,6-branched oligosaccharides: regulation based on the kinetic properties of N-acetylglucosaminyltransferase V.

Human beta1,6-N-acetylglucosaminyltransferase V (GnT-V) was expressed by baculovirus-insect cell system, and the purified recombinant enzyme was kinetically characterized. The data obtained were used to establish the kinetic basis of the substrate specificity toward donor nucleotide sugars, and also revealed that K(m) values for the donors are much higher compared to those of other GlcNAc transferases, the kinetic properties of which have been reported. Because this exceptionally higher K(m) suggests that GnT-V is physiologically present at far from saturated conditions, it would appear that the production of beta1,6-branched oligosaccharide, which is formed by GnT-V, could be regulated in vivo by the concentration of the donor, UDP-GlcNAc, as well as the expression levels of the enzyme. When B16 melanoma cells, which express high levels of GnT-V, were incubated with GlcNAc, the beta1,6-branched oligosaccharide levels were increased, as judged by a lectin blot analysis, in conjunction with an increase in intracellular UDP-GlcNAc. These findings suggest that the level of UDP-GlcNAc can be a critical factor in the production of beta1,6-branched oligosaccharides, for example, by tumor cells, which have been thought to be closely associated with tumor progression and metastasis.

Baculoviridae↗
PubMed2002

Protective effect of a novel and selective inhibitor of inducible nitric oxide synthase on experimental crescentic glomerulonephritis in WKY rats.

BACKGROUND: Nitric oxide (NO) plays important roles in a variety of pathophysiological processes. It has been reported that inducible NO synthase (iNOS) is upregulated in the glomeruli of patients with glomerulonephritis, although there has been no direct evidence that NO generated by iNOS contributes to the progression of glomerulonephritis. ONO-1714, a novel cyclic amidine analog, is a selective inhibitor of iNOS. To elucidate the role of iNOS in the pathogenesis of experimental crescentic glomerulonephritis, we examined the effect of ONO-1714 given to rats with nephrotoxic serum (NTS) nephritis. METHODS: We induced NTS nephritis in Wistar-Kyoto (WKY) rats. These rats were given ONO-1714 or physiological saline intraperitoneally for 14 days using an osmotic pump after intraperitoneal injection with NTS. RESULTS: Glomerular expression of iNOS and urinary excretion of NO metabolites (nitrite/nitrate) were increased in rats after injection of NTS. As compared with the control group, ONO-1714 significantly reduced proteinuria, crescent formation, glomerular infiltration of macrophages and urinary excretion of nitrite/nitrate. CONCLUSION: The present results suggest that NO radicals generated by iNOS contribute to the progression of experimental crescentic glomerulonephritis in WKY rats. The selective iNOS inhibitor ONO-1714 may be beneficial for the treatment of crescentic glomerulonephritis.

Amidines↗
PubMed2002

Oxidative damage due to copper ion and hydrogen peroxide induces GlcNAc-specific cleavage of an Asn-linked oligosaccharide.

Cleavage of an asparagine-linked sugar chain by hydrogen peroxide (H2O2) and a copper salt was investigated. Incubation of a 2-aminopyridine (PA)-labeled biantennary sugar chain, GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-2Manalpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc-PA, with H2O2 and Cu2+ led to formation of four major degradation products. Reversed phase high performance liquid chromatographic analysis coupled with glycosidase digestion indicated that the sugar chain is not randomly degraded but specifically degraded at a GlcNAc residue. Treatment with either of H2O2 or copper alone did not cleave nor degrade the sugar chain to any extent. Electron spin resonance (ESR) spectra obtained using a spin trap reagent were consistent with the generation of OH* or an OH*-like radical by the H2O2/copper salt mixture. The addition of ascorbic acid enhanced this radical generation as well as the degradation of the sugar chain. It was also found that H2O2/Cu2+ destroys the N-acetyl group of the monosaccharide GlcNAc, as judged by a decrease in the ultraviolet absorption spectrum of this group. On the other hand, replacement of copper by Fe2+ caused no cleavage of the sugar chain, although comparable levels of the same radical species were generated. Furthermore, spectrophotometric analysis showed that a GlcNAc-containing sugar chain coordinates to copper but not to iron, and, thus, the coordination appears to play an essential role in the degradation of the sugar chain. These findings suggest that coordination of copper ions to GlcNAc residues localizes the generation of a radical, which cleaves the glycosidic linkage, possibly involving alteration of the N-acetyl group, thereby allowing the GlcNAc-specific cleavage.

Aminopyridines↗
PubMed2002

The possibility of reducing xenoantigen levels with a novel gal 3'-sulfotransferase (GP3ST).

Glycoprotein-3-sulfotransferase (GP3ST) is a key enzyme in downregulating the expression of Galalpha1,3Galbeta1,4GlcNAc-R (the alpha-Gal epitope), via enzymatic competition with an alpha1,3 galactosyltransferase (alpha1,3GT), such as alpha2,6 sialyltransferase (alpha2,6ST). In this study, we report the dominance of GP3ST over alpha1,3GT using transfected pig endothelial cell (PEC) lines. The introduction of the GP3ST gene into PEC suppresses its antigenicity with respect to normal human pooled serum (NHS), including the alpha-Gal epitope and the Hanganutziu-Deicher (H-D) antigen, and, in addition, reduces the susceptibility to NHS in complement-mediated cell lysis. Western and lectin blot analyses of the products of parental PEC and its transfectants indicated that proteins smaller than 66 kDa have a diminished reactivity with NHS and the IB4 lectin. The levels of the alpha-Gal epitope in neutral glycosphingolipids were also decreased in the GP3ST transfectants as detected in thin layer chromatography by immunostaining. These data indicate that GP3ST is very effective in reducing xenoepitope levels.

Animals↗
PubMedDate not supplied

Induction of thioredoxin reductase gene expression by peroxynitrite in human umbilical vein endothelial cells.

Thioredoxin reductase (TR), a flavoprotein, catalyzes the reduction of oxidized thioredoxin in a NADPH-dependent manner, and contains a selenocysteine residue near the C-terminus. TR plays an important role in protecting against oxidative stress and in regulating cell growth and cell death. Constitutive TR expression has been observed in several cell types of the mammalian body, including endothelial cells. The latter are continually exposed to both exogenous and endogenous sources of nitric oxide (NO) and NO-derived species. Reactive nitrogen species (RNS) are associated with pathological events, contributing to the cell and tissue damage accompanying inflammation, atherogenesis and autoimmune diseases. In this study, we report on the effect of peroxynitrite on TR in human umbilical vein endothelial cells (HUVECs). Exposure to the peroxynitrite donor SIN-1 for 1 h resulted in a decrease in TR activity. Interestingly, the activity was completely restored within 24 h. To further examine this mechanism, the expression of TR at the mRNA and protein level was examined. TR mRNA levels were markedly increased by treatment of SIN-1 within 6 h, and TR protein level was also increased after the treatment in HUVECs. These results suggest that the inactivation of TR by peroxynitrite might be involved in the upregulation of the TR gene in HUVECs. Therefore, HUVECs have a unique protective mechanism that allows the maintenance of balance in intracellular redox status via TR induction as an adaptive response to nitrooxidative stress.

Animals↗