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N Taniguchi

Publications and source records attributed to N Taniguchi.

At least 181 records · Page 10Linked to original sources
PubMed1998

[Structure and function of a novel ErbB ligand, NTAK].

A novel member of the epidermal growth factor (EGF) family, the neural and thymus-derived activator for ErbB kinase (NTAK) has been cloned from the cDNA library of a rat pheochromocytoma cell line, PC12 cells and human neuroblastoma cell line, SK-N-SH cells. Four alternative spliced isoforms from rat cDNA have been detected by the methods of RT-PCR. The rat NTAK alpha 2a isoform exhibits 94% identity in its sequence with the human NTAK alpha isoform. Three characteristic Ig-like, EGF-like and hydrophobic domains have been identified in rat and human NTAK molecules. Recombinant NTAK, the soluble 46 kDa form, binds directly to ErbB3 and ErbB4, but not ErbB1 and B2. NTAK, however, transactivates with heterodimer such as ErbB1/B3, B1/B4, B2/B3, B2/B4, and B3/B4. NTAK stimulates the differentiation of MDA-MB-453 cells, derived from blast carcinoma. NTAK competitively inhibits the binding of [125I] NRG-1 to these cells. Thus, NTAK is a new member of the EGF family displaying NRG-1 properties.

Animals↗
PubMed1997

Role of membrane-anchored heparin-binding epidermal growth factor-like growth factor and CD9 on macrophages.

Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) is a potent mitogen for smooth-muscle cells (SMCs) belonging to the EGF family. We have previously determined that HB-EGF is expressed in macrophages and SMCs of human atherosclerotic lesions and that its membrane-anchored precursor, proHB-EGF, also has a juxtacrine mitogenic activity which is markedly enhanced by CD9, a surface marker of lymphohaemopoietic cells. Therefore, when both proHB-EGF and CD9 are expressed on macrophages, they may strongly promote the development of atherosclerosis. In the present study we have investigated the changes in proHB-EGF and CD9 in THP-1 cells during differentiation into macrophages and by the addition of oxidized low-density lipoproteins (OxLDL) and assessed juxtacrine growth activity of THP-1 macrophages for human aortic SMCs. HB-EGF and CD9 at both the mRNA and the protein level were up-regulated after differentiation into macrophages, and further expression of HB-EGF was induced by the addition of OxLDL or lysophosphatidylcholine. Juxtacrine induction by formalin-fixed growth was suppressed to control levels by an inhibitor of HB-EGF and was partially decreased by anti-CD9 antibodies. These results suggest that co-expression of proHB-EGF and CD9 on macrophages plays an important role in the development of atherosclerosis by a juxtacrine mechanism.

Antigens, CD↗
PubMed1997

Remodeling of glycoconjugates on CD44 enhances cell adhesion to hyaluronate, tumor growth and metastasis in B16 melanoma cells expressing beta1,4-N-acetylglucosaminyltransferase III.

Beta1-4 N-acetylglucosaminyltransferase III (GnT-III) synthesizes bisecting N-acetylglucosamine structures on asparagine-linked oligosaccharides. Using B16-hm mouse melanoma cells stably expressing GnT-III activity as positive transfectants, the effect of bisecting N-acetylglucosamine on the function of CD44 was analyzed in association with adhesion to hyaluronate and tumor spread in mice. Transfection of GnT-III caused increased affinity of immunoprecipitated CD44 to erythro-agglutinating phytohemagglutinin, that preferentially recognizes bisecting N-acetylglucosamine, without affecting the surface CD44 amount, indicating an increase in bisecting N-acetylglucosamine residues on CD44 in positive transfectants. CD44-mediated adhesion to immobilized hyaluronate and the binding of fluorescence-labeled hyaluronate to the cell surface were increased in positive transfectants. The enhanced adhesion in positive transfectants was suppressed by the treatment with beta-N-acetylhexosaminidase, indicating that N-acetylglucosamine residues were responsible for the enhanced adhesion. Positive transfectants showed promoted CD44-mediated tumor growth and metastatic development in the spleen after subcutaneous inoculation into mice. These results indicate that glycosylation of CD44 due to GnT-III causes enhanced adhesion to hyaluronate, local tumor growth and metastatic growth in spleen, suggesting that the CD44-mediated adhesion and tumor spread can be modified through introduction of a glycosyltransferase gene.

Acetylglucosamine↗
PubMed1997

Expression of heparin-binding epidermal growth factor-like growth factor during pancreas development. A potential role of PDX-1 in transcriptional activation.

The development of the pancreas appears to be regulated by various growth factors. We report here the expression of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) in the developing pancreas. Immunostaining of fetal and neonatal rat pancreata, in which endocrine cells are visible as cell clusters often associated with primitive ducts or ductular cells, revealed that most of the cluster-forming cells and primitive ducts or ductular cells express HB-EGF protein. In contrast, the exocrine pancreas lacked HB-EGF expression. Based on findings that the expression pattern was similar to that of the homeodomain-containing transcription factor PDX-1 (IDX-1/STF-1/IPF1) and that the regulatory region of the HB-EGF gene contained sequences similar to the PDX-1-binding A element, we examined whether PDX-1 could be a potential activator of HB-EGF gene expression. The results of reporter gene analyses suggested that the HB-EGF gene promoter is PDX-1-responsive and that the activity of the promoter in pancreatic beta cell-derived betaTC1 cells depends on the PDX-1 binding site-like sequences. Gel-mobility shift analyses using an anti-PDX-1 antibody indicated that PDX-1 is a specific and dominant binding factor for an A element-like sequence in the HB-EGF gene. These observations suggest the possible involvement of HB-EGF in pancreas development. While PDX-1 is essential for pancreas development, HB-EGF may function as a mediator of PDX-1 and thus be involved in the development of the endocrine pancreas.

Animals↗
PubMed1997

Induction of manganese superoxide dismutase by thyroid stimulating hormone in rat thyroid cells.

Alterations in the superoxide dismutase (SOD) content of thyroid tissues occurring in association with thyroid dysfunction have been reported. In this study, the Mn-SOD content was found to increase in thyroid tissues of rats administered thyroid stimulating hormone (TSH) and in thyrocytes cultured in medium supplemented with TSH. Furthermore, in the thyroid glands of rats whose serum TSH level was elevated by inhibiting the synthesis of T3 and T4 by 6-methyl-2-thiouracil, the Mn-SOD increased as the TSH concentration increased. In the cultured thyrocytes, the increase in Mn-SOD induced by TSH was inhibited by the C-kinase inhibitor H7. These findings suggest the induction of Mn-SOD by TSH in thyroid cells and point to a role of C-kinase in this process, thereby indicating that a close relationship exists between the serum TSH level and the change in Mn-SOD content in thyrocytes with thyroid dysfunction.

Animals↗
PubMed1997

The effect of cilostazol, a cyclic nucleotide phosphodiesterase III inhibitor, on heparin-binding EGF-like growth factor expression in macrophages and vascular smooth muscle cells.

Heparin-binding EGF-like growth factor (HB-EGF) is a mitogen for smooth muscle cells (SMC) and is detected in SMC and macrophages in atherosclerotic plaques, suggesting that HB-EGF may be associated with the pathogenesis of atherosclerosis. The present study indicates that cilostazol, a phosphodiesterase III inhibitor, suppresses the expression of HB-EGF in rat aortic SMC and in U-937 cells, a macrophage-like cell line, stimulated by lipopolysaccharide. Further, cilostazol diminished the induction of HB-EGF mRNA by methylglyoxsal, which is a reactive dicarbonyl metabolite produced as the result of a glycation reaction and which might be associated with macroangiopathy caused by hyperglycemia. Cilostazol suppressed the production of HB-EGF protein in the conditioned medium of SMC. These data suggest that cilostazol might act by suppressing the progression of atherogenesis by means of suppressing the expression of HB-EGF in SMC and macrophages.

Animals↗
PubMed1997

Expression of alpha1-6 fucosyltransferase in rat tissues and human cancer cell lines.

GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha1-6 fucosyltransferase (alpha1-6FucT) catalyzes the transfer of a fucosyl residue from GDP-fucose to the asparagine-linked GlcNAc residue of complex N-glycans via alpha1-6 linkage. These oligosaccharide structures are essential for the attachment of polysialic acid to the neural-cell-adhesion molecule, and its levels are useful for the differential diagnosis of hepatocellular carcinomas with respect to the microheterogeneity of alpha-fetoprotein. We have been successful in the purification and cDNA cloning of alpha1-6FucT from porcine brain and from a human gastric-cancer cell line. In the present study, mRNA expression of alpha1-6FucT in various rat tissues and human cancer cell lines was examined, along with the expression of alpha1-6FucT mRNA and the induction by treatment with several cytokines. Northern-blot analysis indicated high expression levels of alpha1-6FucT in brain and gastrointestinal-tract tissues of normal rats, as well as for a number of lung-cancer, gastric-cancer and colon-cancer cell lines. Although various cytokines did not induce alpha1-6FucT mRNA, differentiation of a tumor cell enhanced the mRNA by 2- to 3-fold. These results may provide new insight into studies on alpha1-6FucT in terms of carcinogenesis or differentiation.

Animals↗
PubMed1997

Purification and characterization of UDP-N-acetylglucosamine: alpha1,3-D-mannoside beta1,4-N-acetylglucosaminyltransferase (N-acetylglucosaminyltransferase-IV) from bovine small intestine.

A new beta1,4-N-acetylglucosaminyltransferase (GnT) which involves in branch formation of Asn-linked complex-type sugar chains has been purified 224,000-fold from bovine small intestine. This enzyme requires divalent cations, such as Mn2+, and catalyzes the transfer of GlcNAc from UDP-GlcNAc to biantennary oligosaccharide and produces triantennary oligosaccharide with the beta1-4-linked GlcNAc residue on the Manalpha1-3 arm. The purified enzyme shows a single band of Mr 58,000 and behaves as a monomer. The substrate specificity demonstrated that the beta1-2-linked GlcNAc residue on the Manalpha1-3 arm (GnT-I product) is essential for the enzyme activity. beta1-4-Galactosylaion to this essential beta1-2-linked GlcNAc residue or N-acetylglucosaminylation to the beta-linked Man residue (bisecting GlcNAc, GnT-III product) blocks the enzyme action, while beta1-6-N-acetylglucosaminylation to the Manalpha1-6 arm (GnT-V product) increases the transfer. Based on these findings, we conclude that the purified enzyme is UDP-N-acetylglucosamine:alpha-3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV (GnT-IV), that has been a missing link on biosynthesis of complex-type sugar chains.

Animals↗
PubMed1997

The oxidation of selenocysteine is involved in the inactivation of glutathione peroxidase by nitric oxide donor.

Glutathione peroxidase (GPx) was inactivated by S-nitroso-N-acetyl-D, L-penicillamine (SNAP), a nitric oxide donor (Asahi, M., Fujii, J., Suzuki, K., Seo, H. G., Kuzuya, T., Hori, M., Tada, M., Fujii, S., and Taniguchi, N. (1995) J. Biol. Chem. 270, 21035-21039). The structural basis of the inactivation was studied. We also show that 3-morpholinosydnonimine N-ethylcarbamide, a peroxynitrite precursor, as well as synthetic peroxynitrite also inactivated bovine GPx. The degree of incorporation of a sulfhydryl reagent, n-octyldithionitrobenzoic acid, into GPx decreased after pretreatment with SNAP as evidenced by mass spectrometry. To identify the modification site of this enzyme by SNAP, both SNAP-pretreated and untreated GPxs were reacted with n-octyldithionitrobenzoic acid and digested with lysylendopeptidase, and the resulting peptides were subjected to mass spectrometry. This technique identified a bridge between two peptides, one of which contains Sec45 at the catalytic center and Cys74, and the other contains Cys91. Although there are two possible combinations, selenocysteine 45 (Sec45) and Cys91 or Cys74 and Cys91, the tertiary structure of GPx indicates that a cross-link between Sec45 and Cys91 is more feasible. This is consistent with the experimental evidence that SNAP specifically inactivates GPx, in which Sec45 forms the catalytic center. Thus, we conclude that SNAP mainly oxidized Sec45 to form a selenenyl sulfide (Se-S) with a free thiol, leading to the inactivation of the enzyme. These data suggest that nitric oxide and its derivatives directly inactivate GPx in a specific manner via the production of a selenenyl sulfide, resulting in an increase in intracellular peroxides that are responsible for cellular damage.

Amino Acid Sequence↗
PubMed1997

Selective induction of heparin-binding epidermal growth factor-like growth factor by methylglyoxal and 3-deoxyglucosone in rat aortic smooth muscle cells. The involvement of reactive oxygen species formation and a possible implication for atherogenesis in diabetes.

Methylglyoxal (MG) and 3-deoxyglucosone (3-DG), reactive dicarbonyl metabolites in the glyoxalase system and glycation reaction, respectively, selectively induced heparin-binding epidermal growth factor (HB-EGF)-like growth factor mRNA in a dose- and time-dependent manner in rat aortic smooth muscle cells (RASMC). A nuclear run-on assay revealed that the dicarbonyl may regulate expression of HB-EGF at the transcription level. The dicarbonyl also increased the secretion of HB-EGF from RASMC. However, platelet-derived growth factor, another known growth factor of smooth muscle cells (SMC), was not induced by both dicarbonyls. The dicarbonyl augmented intracellular peroxides prior to the induction of HB-EGF mRNA as judged by flow cytometric analysis using 2',7'-dichlorofluorescin diacetate. N-Acetyl-L-cysteine and aminoguanidine suppressed both dicarbonyl-increased HB-EGF mRNA and intracellular peroxide levels in RASMC. DL-Buthionine-(S, R)-sulfoximine increased the levels of 3-DG-induced HB-EGF mRNA. Furthermore, hydrogen peroxide alone also induced HB-EGF mRNA in RASMC. These results indicate that MG and 3-DG induce HB-EGF by increasing the intracellular peroxide levels. In addition, the pretreatment with 12-O-tetra-decanoylphorbol-13-acetate failed to alter dicarbonyl-induced HB-EGF mRNA expression in RASMC, suggesting that the signal transducing mechanism is not mediated by protein kinase C. Since HB-EGF is known as a potent mitogen for smooth muscle cells and is abundant in atherosclerotic plaques, the induction of HB-EGF by MG and 3-DG, as well as the concomitant increment of intracellular peroxides, may trigger atherogenesis during diabetes.

Acetylcysteine↗
PubMed1997

Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach.

The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.

Amphiregulin↗
PubMed1997

Significant downregulation of the major swine xenoantigen by N-acetylglucosaminyltransferase III gene transfection.

Introduction of the beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene into swine endothelial cells (SEC) reduced their susceptibility to normal human serum (NHS) in complement-mediated cell lysis and also suppressed the antigenicity to human natural antibodies as evidenced by flow cytometric analysis, as well as Griffonia simplicifolia 1 isolectin (1B4 lectin) binding to the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (the alpha-galactosyl epitope). Western blot analysis indicated that proteins smaller than 66 kDa had diminished reactivity to NHS and 1B4 lectin. GnT-III, a key enzyme involved in branch formation of N-linked sugars, was found to downregulate the expression of xenoantigen, suggesting that this approach may be of value in clinical xenotransplantation in the future.

Animals↗
PubMed1997

Membrane-anchored heparin-binding epidermal growth factor-like growth factor acts as a tumor survival factor in a hepatoma cell line.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which belongs to the EGF family, is produced as a membrane-anchored form (pro-HB-EGF) and later processed to a soluble form (sHB-EGF). It is known that high expression of pro-HB-EGF occurs in hepatoma tissues, although its biological meaning remains unknown. We established two types of hepatoma cell lines (AH66tc), which stably produce pro-HB-EGF and sHB-EGF, respectively. While sHB-EGF-producing cells (sHB-AH) showed rapid growth, pro-HB-EGF-producing cells (pHB-AH) showed markedly suppressed cell growth as compared with the parental cells. Transforming growth factor beta or serum-starved conditions induced apoptosis of mock and sHB-AH as well as the parental cells, but not of pHB-AH. The resistance to apoptosis upon serum-starved treatment was correlated with an increase in the rate of the G1 phase in the cell cycle due to up-regulation of the cyclin-dependent kinase inhibitor p21. The mechanism underlying this resistance of pHB-AH to apoptosis was thought to be related to the prolonged half-life of the EGF receptor followed by continuous phosphorylation of the tyrosine residues. These observations demonstrate a unique function of pro-HB-EGF that is not observed for the mature form and show that pro-HB-EGF may act as a tumor survival factor in hepatoma cells.

Animals↗
PubMed1997

Overexpression of N-acetylglucosaminyltransferase III disrupts the tyrosine phosphorylation of Trk with resultant signaling dysfunction in PC12 cells treated with nerve growth factor.

beta-1,4-N-Acetylglucosaminyltransferase III (GnT-III: EC 2.4.1.144) is a pivotal glycosyltransferase which participates in branch formation by catalysis of the synthesis of a bisecting GlcNAc structure in N-glycans. These structures are thought to be one of the unique features of the N-glycans of neural tissues. To examine the intracellullar role of GnT-III expression and its product in neural cells, its gene was overexpressed in rat pheochromocytoma PC12 cells which normally express a low level of GnT-III. In the GnT-III gene-transfected cells, lectin blot analysis showed that some glycoproteins showed increased levels of bisecting GlcNAc structures. Following treatment with nerve growth factor (NGF) the control cells showed neurite outgrowth for differentiation whereas the transfectants showed no morphological response or change in the rate of cell growth. Transient tyrosine phosphorylation of the Trk/NGF receptor was detected at 5-15 min after NGF treatment in control cells, but not detected in the GnT-III gene-transfected cells despite the intact binding of NGF to the cells. Moreover the dimerization of Trk with NGF treatment was not induced in the GnT-III transfectant as compared with the dimerization seen in control cells. These results indicate that overexpression of GnT-III gene in PC12 cells affects some functions of glycoprotein receptors such as Trk by alteration of N-glycan structures, and results in changes in the intracellular signaling pathway of tyrosine phosphorylation modified by NGF.

Animals↗