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941.
Matsui T Kondo T Nishita Y Itadani S Nakatani S Omawari N Sakai M Nakazawa S Ogata A Mori H Terai K Kamoshima W Ohno H Obata T Nakai H Toda M 《Bioorganic & medicinal chemistry》2002,10(12):3757-3786
Discovery of new chemical leads of inhibitors for TNF-alpha production starting from the chemical modification of 1 is reported. Further biological studies of 1 to disclose the site of its action strongly suggested that 1 inhibits LPS-induced TNF-alpha expression in the liver and spleen of mice. Structure-activity relationships (SARs) are also discussed and full details including the chemistry are reported. 相似文献
942.
Matsui Y Ishikawa J Kamitakahara H Takano T Nakatsubo F 《Carbohydrate research》2005,340(7):1403-1406
6-Amino-6-deoxycellulose (4) was synthesized from cellulose by three reaction steps, namely bromination at C-6, displacement of bromine by azide ion, and reduction of the azide group to amino group, in 67% overall yield. The 13C NMR spectrum of compound 4 supports the expected structure for 6-amino-6-deoxycellulose. The degree of substitution of compound 4 was 0.96. 相似文献
943.
Wallerian degeneration involves Rho/Rho-kinase signaling 总被引:6,自引:0,他引:6
Yamagishi S Fujitani M Hata K Kitajo K Mimura F Abe H Yamashita T 《The Journal of biological chemistry》2005,280(21):20384-20388
Local axon degeneration is a common pathological feature of many neurodegenerative diseases, whereas the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed "Wallerian degeneration," as a model to examine the possible involvement of Rho. Nogo-66, a myelin-derived inhibitor of axon regeneration, significantly accelerated axon degeneration of the dorsal root ganglion explant in vitro, whereas inhibiting Rho-kinase activity abolished the effect. Rho activation was observed in the distal part of the injured axons after spinal cord injury. We demonstrate that degeneration of the injured cortico-spinal axons was significantly retarded by a Rho-kinase inhibitor in vivo. Our findings suggest that inhibiting the signaling pathway may retard axon degeneration in pathological conditions. 相似文献
944.
Drosophila PTEN (dPTEN) plays indispensable roles in the development of Drosophila melanogaster by controlling cell size and number. Although three potential spliced forms of dPTEN have been isolated, functional distinction among these forms remains elusive. In this study, we demonstrate that all spliced forms of dPTEN dephosphorylate phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)); however, PI(3,4,5)P(3)-dependent activation of Drosophila Akt is suppressed specifically by one of three spliced forms, dPTEN3. Further, dPTEN3 dramatically changes its expression during the Drosophila development, while the other forms are expressed throughout the development. Our results suggest that dPTEN3 is the predominant spliced form that participates in PI(3,4,5)P(3)-mediated signaling pathways. 相似文献
945.
Sugiura F Kitoh H Ishiguro N 《Biochemical and biophysical research communications》2004,316(1):233-239
Osteogenic potential of serially passaged rat bone marrow derived mesenchymal stem cells (BMCs) was evaluated for clinical feasibility. Osteogenic differentiation in vitro was evaluated by means of the concentration and mRNA expression of alkaline phosphatase and osteocalcin. For in vivo osteogenesis, BMCs in various degrees of differentiation were implanted into the athymic mice. Although elevated levels of osteogenic markers were prominent in the less passaged BMCs continuously cultured with osteogenic supplements (OS group), they decreased with passaging. Similar to the in vitro experiments, abundant bone and cartilage formations inside the membrane were observed in the P0 through P2 cells of the OS group. In the P3 cells, however, the chambers were filled with fibrous tissues showing the failure of osteogenesis. Establishment of the culture conditions that permit the rapid expansion of BMCs while retaining their potential for differentiation will be required for future clinical applications. 相似文献
946.
Bekker EG Creagh AL Sanaie N Yumoto F Lau GH Tanokura M Haynes CA Murphy ME 《Biochemistry》2004,43(28):9195-9203
Ferric binding protein in Neisseria gonorrhoeae (nFbpA) transports iron from outer membrane receptors for host proteins across the periplasm to a permease in an alternative pathway to the use of siderophores in some pathogenic bacteria. Phosphate and nitrilotriacetate, both at pH 8, and vanadate at pH 9 are shown to be synergistic in promoting ferric binding to nFbpA, in contrast to carbonate and sulfate. Interestingly, only phosphate produces the fully closed conformation of nFbpA as defined by native electrophoresis. The role of phosphate was probed by constructing three mutants: Q58E, Q58R, and G140H. The anion and iron binding properties of the Q58E mutant are similar to the wild-type protein, implying that one phosphate oxygen is a hydrogen bond donor and may in part define the specificity of nFbpA for phosphate over sulfate. Phosphate is a weakly synergistic anion in the Q58R and G140H mutants, and these mutants do not form completely closed structures. Ferric binding was investigated by both isothermal titration and differential scanning calorimetry. The apparent affinity of nFbpA for iron in a solution of 30 mM citrate is 1 order of magnitude larger in the presence (K(app)= 1.7 x 10(5) M(-1)) of phosphate than in its absence (K(app) = 1.6 x 10(4) M(-1)) at pH 7. Similar results were obtained at pH 8. This increase in affinity with phosphate as well as the formation of closed structure allows nFbpA to compete for free ferric ions in solution and suggests that ferric binding to nFbpA is regulated by the synergistic phosphate anion at sites of iron uptake. 相似文献
947.
Takeuchi H Niwa J Hishikawa N Ishigaki S Tanaka F Doyu M Sobue G 《Journal of neurochemistry》2004,89(1):64-72
Abstract Dorfin is a RING-finger type ubiquitin ligase for mutant superoxide dismutase 1 (SOD1) that enhances its degradation. Mutant SOD1s cause familial amyotrophic lateral sclerosis (FALS) through the gain of unelucidated toxic properties. We previously showed that the accumulation of mutant SOD1 in the mitochondria triggered the release of cytochrome c, followed by the activation of the caspase cascade and induction of neuronal cell death. In the present study, therefore, we investigated whether Dorfin can modulate the level of mutant SOD1 in the mitochondria and subsequent caspase activation. We showed that Dorfin significantly reduced the amount of mutant SOD1 in the mitochondria, the release of cytochrome c and the activation of the following caspase cascade, thereby preventing eventual neuronal cell death in a neuronal cell model of FALS. These results suggest that reducing the accumulation of mutant SOD1 in the mitochondria may be a new therapeutic strategy for mutant SOD1-associated FALS, and that Dorfin may play a significant role in this. 相似文献
948.
Nakai M Obata M Sekiguchi F Kato M Shiro M Ichimura A Kinoshita I Mikuriya M Inohara T Kawabe K Sakurai H Orvig C Yano S 《Journal of inorganic biochemistry》2004,98(1):105-112
Two chargeless VO(IV) complexes with 3-hydroxypyridine-2-carboxylic acid (H2hpic), [VO(Hhpic-O,O)(Hhpic-O,N)(H2O)].3H2O (1) and the cyclic tetramer [(VO)4(mu-(hpic-O,O',N))4(H2O)4].8H3O (2), have been synthesized and characterized by elemental analysis, mass, infrared, electronic absorption, electron spin resonance (ESR) spectroscopies, and X-ray crystallography. Their coordination structures are similar to each other (and 1 is readily transformed into 2), but are quite different from that of bis(pyridine-2-carboxylato)oxovanadium(IV). The magnetic susceptibility of 2 indicates the presence of a weak ferromagnetic intramolecular interaction between the V atoms at low temperature, in addition to a weak antiferromagnetic intermolecular interaction. The ESR signal of 2 was broad, while 1 showed an eight-line hyperfine splitting pattern due to coupling of the unpaired electron with the 51V nucleus (I=7/2). The ESR spectrum and cyclic voltammogram of 2 clearly show that the cyclic tetramer remains intact in solution. The insulinomimetic activity of 1 and 2 was evaluated by means of in vitro measurements of the inhibition of free fatty acid release from epinephrine-treated isolated rat adipocytes. While 1 exerted higher insulinomimetic activity than VOSO4, the activity of 2 was significantly lower than that of VOSO4. Hence 2 appears to retain its cyclic structure during the in vitro test. These results indicate that the rational ligand design for VO complexes might be a promising approach to obtain superior insulinomimetic activity. 相似文献
949.
MAPK activation in nociceptive neurons and pain hypersensitivity 总被引:22,自引:0,他引:22
950.
Yamamoto T Yoshimura M Yamaguchi F Kouchi T Tsuji R Saito M Obata A Kikuchi M 《Bioscience, biotechnology, and biochemistry》2004,68(8):1706-1711
The anti-allergic activity of a tomato extract was studied by using an in vitro histamine-release assay. The tomato skin extract exerted the strongest inhibition of histamine release. Chlorogenic acid, rutin and naringenin were identified in the 60% ethanol extract of tomato skin. However, the extract contained an unknown compound which strongly inhibited histamine release. This active compound in tomato skin was identified as naringenin chalcone (trans-2'4'6'4-tetrahydroxychalcone). Naringenin chalcone inhibited histamine release with an IC(50) value of 68 microg/ml. The anti-allergic activity of the tomato skin extract was next investigated by the in vivo mouse ear-swelling response. We found that naringenin chalcone showed the strongest inhibitory effect of the polyphenols of the tomato skin extract. These results indicate that a tomato skin extract could inhibit allergic reactions. 相似文献