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111.
Islam MS Kitagawa M Imoto M Kitahara T Watanabe H 《Bioscience, biotechnology, and biochemistry》2006,70(10):2523-2528
Gerfelin, an inhibitor of human geranylgeranyl diphosphate (GGPP) synthase that has been isolated from a culture broth of Beauveria felina QN22047, was synthesized in 4 and 3 steps starting from 2,4-dihydroxy-6-methylbenzoic acid and 3,4,5-trihydroxytoluene, respectively. An effective ligand, 2-(di-tert-butylphosphino)biphenyl, was used in the palladium-catalyzed diaryl ether-forming reaction. Five analogous compounds of gerfelin were also synthesized for a study of the structure-activity relationship. 相似文献
112.
Regulation of fibroblast growth factor-23 signaling by klotho 总被引:20,自引:0,他引:20
Kurosu H Ogawa Y Miyoshi M Yamamoto M Nandi A Rosenblatt KP Baum MG Schiavi S Hu MC Moe OW Kuro-o M 《The Journal of biological chemistry》2006,281(10):6120-6123
The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23. 相似文献
113.
Saita Y Kodama E Orita M Kondo M Miyazaki T Sudo K Kajiwara K Matsuoka M Shimizu Y 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(5):3116-3122
The chemokine receptor CCR5 is an attractive target for HIV-1 drug development, as individuals whose cells lack surface CCR5 expression are highly resistant to HIV-1 infection. CCR5 ligands, such as CCL5/RANTES, effectively inhibit HIV-1 infection by competing for binding opportunities to the CCR5 and inducing its internalization. However, the inherent proinflammatory activity of the chemotactic response of CCR5 ligands has limited their clinical use. In this study, we found that a novel small molecule, functionally selective CCR5 agonist, 2,2-dichloro-1-(triphenylphosphonio)vinyl formamide perchlorate (YM-370749), down-modulates CCR5 from the cell surface without inducing a chemotactic response and inhibits HIV-1 replication. In molecular docking studies of YM-370749 and a three-dimensional model of CCR5 based on the rhodopsin crystal structure as well as binding and functional studies using various CCR5 mutants, the amino acid residues necessary for interaction with YM-370749 were marked. These results provide a structural basis for understanding the activation mechanism of CCR5 and for designing functionally selective agonists as a novel class of anti-HIV-1 agents. 相似文献
114.
115.
Akeda K Hirata H Matsumoto M Fukuda A Tsujii M Nagakura T Ogawa S Yoshida T Uchida A 《Plastic and reconstructive surgery》2006,117(4):1194-203; discussion 1204-5
116.
Curious low-temperature solubility of cellulose triacetates (CTA; here we use nominally "CTA," but the sample still contains 7% of C-6 position hydroxyls) in an organic solvent, methyl acetate (MA), was studied by a newly designed low-temperature type of DLS apparatus, which enabled for the first time to investigate the structural change of CTA in solution from 45 degrees C down to -100 degrees C. A molecularly dissolved CTA was found to coexist with three types of self-assemblies over all the temperature ranges except for the three specific temperatures T* of 30, -10, and -75 degrees C. However, these multiple self-assemblies are not in real thermodynamic equilibrium but in a metastable state, which could be stabilized effectively by the intermolecular hydrogen bonding (HB) with the help of the dipole interaction at low temperatures. In more detail, with decreasing temperature, these assemblies performed the structural reorganization drastically at three T*'s and would finally be frozen in a physical gel structure at -99 degrees C; around the freezing temperature of MA, CTA molecules could be trapped homogeneously in the frozen MA. The crucial role in such structural reorganizations is played by the balance between the intermolecular HB and the dipole interaction worked in the highly electronegative solvent. Because these interactions, which are mediated by the solvent electronegativity, change drastically with temperature, they result in the control of not only the single CTA chain conformation (= the intramolecular HB) but also the binding ways of the intermolecular HBs between CTA molecules and they induce multitudinous metastable structures in solution. Here it is noted that HB could work mainly between the C-6 position hydroxyls in the anhydroglucose units of CTA and are essentially effective at low temperatures. 相似文献
117.
Altered localization of amyloid precursor protein under endoplasmic reticulum stress 总被引:2,自引:0,他引:2
Kudo T Okumura M Imaizumi K Araki W Morihara T Tanimukai H Kamagata E Tabuchi N Kimura R Kanayama D Fukumori A Tagami S Okochi M Kubo M Tanii H Tohyama M Tabira T Takeda M 《Biochemical and biophysical research communications》2006,344(2):525-530
Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress on amyloid-beta peptide (Abeta) generation. In this study, we found that ER stress altered the localization of amyloid precursor protein (APP) from late compartments to early compartments of the secretory pathway, and decreased the level of Abeta 40 and Abeta 42 release by beta- and gamma-cutting. Transient transfection with BiP/GRP78 also caused a shift of APP and a reduction in Abeta secretion. It was revealed that the ER stress response facilitated binding of BiP/GRP78 to APP, thereby causing it to be retained in the early compartments apart from a location suitable for the cleavages of Abeta. These findings suggest that induction of BiP/GRP78 during ER stress may be one of the regulatory mechanisms of Abeta generation. 相似文献
118.
Morita M Okuno M Susilo ES Setyo BP Martarini D Harnadi L Takemura A 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2006,143(3):361-367
Sperm of most fresh water teleosts become motile when released into the hypotonic fresh water environment, but the role of osmolality and Ca2+ on sperm motility is not clear. Osmotic pressure and Ca2+ concentrations increase from fresh water to brackish water. Java carp Puntius javanicus and catfish Clarias batrachus live and reproduce only in fresh water. On the other hand, goby Oxyeleotris marmorata can acclimate and reproduce from fresh water to brackish water. In the present study, sperm motility and trajectory were compared among these three Indonesian endemic species. Sperm of Java carp, goby, and catfish begun to move in the hypotonic condition (< 200 mOsm/kg). However, the response to Ca2+ was different among these teleosts. In the presence of Ca2+, Java carp sperm swam in circular paths and immediately become quiescent, suggesting that Java carp sperm motility is activated in hypotonic aquatic environment without Ca2+. Goby sperm swam straightforward in the presence or absence of Ca2+. Percentages of motile sperm increased in 100-200 mOsm/kg but suppressed by removal of Ca2+. Regarding sperm motility and trajectory, no response was found in catfish sperm. These results suggest that a response to Ca2+ is different among sperm of the three species and suited to their habitat. 相似文献
119.
Ishikawa S Kuno A Tanno M Miki T Kouzu H Itoh T Sato T Sunaga D Murase H Miura T 《American journal of physiology. Heart and circulatory physiology》2012,302(12):H2536-H2544
Sarcolemmal connexin-43 (Cx43) and mitochondrial Cx43 play distinct roles: formation of gap junctions and production of reactive oxygen species (ROS) for redox signaling. In this study, we examined the hypothesis that Cx43 contributes to activation of a major cytoprotective signal pathway, phosphoinositide 3-kinase (PI3K)-Akt-glycogen synthase kinase-3β (GSK-3β) signaling, in cardiomyocytes. A δ-opioid receptor agonist {[d-Ala(2),d-Leu(5)]enkephalin acetate (DADLE)}, endothelin-1 (ET-1), and insulin-like growth factor-1 (IGF-1) induced phosphorylation of Akt and GSK-3β in H9c2 cardiomyocytes. Reduction of Cx43 protein to 20% of the normal level by Cx43 small interfering RNA abolished phosphorylation of Akt and GSK-3β induced by DADLE or ET-1 but not that induced by IGF-1. DADLE and IGF-1 protected H9c2 cells from necrosis after treatment with H(2)O(2) or antimycin A. The protection by DADLE or ET-1, but not that by IGF-1, was lost by reduction of Cx43 protein expression. In contrast to Akt and GSK-3β, PKC-ε, ERK and p38 mitogen-activated protein kinase were phosphorylated by ET-1 in Cx43-knocked-down cells. Like diazoxide, an activator of the mitochondrial ATP-sensitive K(+) channel, DADLE and ET-1 induced significant ROS production in mitochondria, although such an effect was not observed for IGF-1. Cx43 knockdown did not attenuate the mitochondrial ROS production by DADLE or ET-1. Cx43 was coimmunoprecipitated with the β-subunit of G protein (Gβ), and knockdown of Gβ mimicked the effect of Cx43 knockdown on ET-1-induced phosphorylation of Akt and GSK-3β. These results suggest that Cx43 contributes to activation of class I(B) PI3K in PI3K-Akt-GSK-3β signaling possibly as a cofactor of Gβ in cardiomyocytes. 相似文献
120.
Particular alkaloids produced by Neotyphodium endophytes show toxicity to invertebrates. Italian ryegrass (Lolium multiflorum Lamarck) cultivars and strains that are symbiotic with Neotyphodium endophytes have been recently established in Japan. N. uncinatum-infected Italian ryegrass lines accumulate N-formylloline, a type of loline alkaloid (1-aminopyrrolizidine) showing neurotoxicity to herbivorous insects. This study investigated the toxicity of N-formylloline and resistance of N. uncinatum-infected Italian ryegrass to vascular-sap feeding Clypeorrhynchan pests. When four vascular-sap feeding insects: Laodelphax striatellus (Fallén) (Homoptera: Delphacidae), Sogatella furcifera (Horváth) (Homoptera: Delphacidae), Cicadulina bipunctata (Melichar) (Homoptera: Cicadellidae), and Nephotettix cincticeps (Uhler) (Homoptera: Cicadellidae) fed on N. uncinatum-infected Italian ryegrass, significant decreases in survival rate were observed for three phloem-sap feeders but not for a xylem-sap feeder, N. cincticeps. This result suggests an uneven distribution of N-formylloline among plant tissues. A potency assay for N-formylloline using a Parafilm feeding sachet and a quantitative analysis of N-formylloline in plant showed a concentration-dependent lethal effect of N-formylloline on all four tested vascular-sap feeders. Our results strongly suggest that N. uncinatum-infected plants can control some Clypeorrhynchan pests in crop fields. 相似文献