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991.
Moritaka H Sawamura S Kobayashi M Kitade M Nagata K 《Bioscience, biotechnology, and biochemistry》2012,76(3):429-435
The relation between the rheological properties and the swallowing characteristics of vegetable juices fortified with 0-30.0% carrot puree (CP) was evaluated. The apparent viscosity of vegetable juices increased with increasing CP concentrations, and a increases in yield stress were observed at and above 17.5% CP. In a sensory evaluation, texture perceived in the oral cavity varied as between vegetable juices with >17.5% CP and those with <12.5% CP. The maximum velocity in the pharyngeal region was classified into three same-quality subgroups: vegetable juices with 0-12.5% CP, with 10.0-25.0% CP, and with 17.5-30.0% CP. It significantly decreased with increasing CP concentrations. 相似文献
992.
The small GTPase RhoA is a molecular switch in various extracellular signals. Rho-kinase/ROCK/ROK, a major effector of RhoA, regulates diverse cellular functions by phosphorylating cytoskeletal proteins, endocytic proteins, and polarity proteins. More than twenty Rho-kinase substrates have been reported, but the known substrates do not fully explain the Rho-kinase functions. Herein, we describe the comprehensive screening for Rho-kinase substrates by treating HeLa cells with Rho-kinase and phosphatase inhibitors. The cell lysates containing the phosphorylated substrates were then subjected to affinity chromatography using beads coated with 14-3-3 protein, which interacts with proteins containing phosphorylated serine or threonine residues, to enrich the phosphorylated proteins. The identities of the molecules and phosphorylation sites were determined by liquid chromatography tandem mass spectrometry (LC/MS/MS) after tryptic digestion and phosphopeptide enrichment. The phosphorylated proteins whose phosphopeptide ion peaks were suppressed by treatment with the Rho-kinase inhibitor were regarded as candidate substrates. We identified 121 proteins as candidate substrates. We also identified phosphorylation sites in Partitioning defective 3 homolog (Par-3) at Ser143 and Ser144. We found that Rho-kinase phosphorylated Par-3 at Ser144 both in vitro and in vivo. The method used in this study would be applicable and useful to identify novel substrates of other kinases. 相似文献
993.
We developed a method to convert a nucleoside 5'-H-boranophosphonate monoester into the corresponding nucleoside 5'-boranophosphorothioate monoester through temporary protection of the H-boranophosphonate monoester moiety as a diester with 9-fluorenylmethanol, subsequent sulfurization of the P-H group and removal of the 9-fluorenylmethyl group. Although the isolation of the resultant boranophosphorothioate monoester was found to be difficult due to instability of the compound, this new method proved to be useful to synthesize some conjugates of the nucleoside 5'-boranophosphorothioate with other biomolecules, such as cholesterol and an amino acid. 相似文献
994.
Setoguchi M Iimura S Sugimoto Y Yoneda Y Chiba J Watanabe T Muro F Iigo Y Takayama G Yokoyama M Taira T Aonuma M Takashi T Nakayama A Machinaga N 《Bioorganic & medicinal chemistry》2012,20(3):1201-1212
For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido)phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido)phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse α(4) antibody (R1-2). 相似文献
995.
Fukuhara K Ishikawa K Yasuda S Kishishita Y Kim HK Kakeda T Yamamoto M Norii T Ishikawa T 《Cellular and molecular neurobiology》2012,32(6):971-977
Neuropathic pain concurrent with mood disorder from peripheral nerve injury is a serious clinical problem that significantly affects quality of life. Recent studies have suggested that a lack of brain-derived neurotrophic factor (BDNF) in the limbic system may cause this pain-emotion. BDNF is induced in cultured neurons by 4-methylcatechol (4-MC), but the role of 4-MC-induced BDNF in pain-emotion is poorly understood. Thus, we assessed the possible involvement of BDNF in brain in depression-like behavior during chronic pain following peripheral nerve injury. In addition, we examined whether intracerebroventricular (i.c.v.) 4-MC prevents chronic pain in rats and produces an antidepressant effect. Sprague-Dawley rats implanted intracerebroventricularly with a PE-10 tube were subjected to chronic constriction injury (CCI). Pain was assessed by a reduction in paw withdrawal latency (PWL) to heat stimuli after CCI. We also used a forced swimming testing (FST; time of immobility, in seconds) from day 14 to day 21 after CCI. Modulation of pain and emotional behavior was performed by injection of PD0325901 (a MEK1/2 inhibitor). 4-MC (100 nM) was continuously administered i.c.v. for 3 days during the period from day 14 to day 21 after CCI. To block analgesic and antidepressant effects, anti-BDNF antibody or K252a (a TrkB receptor inhibitor) was injected in combination with 4-MC. Naloxone was also coadministered to confirm the analgesic effect of 4-MC. During the chronic stage after CCI, the rats showed a sustained decrease in PWL (thermal hyperalgesia) associated with extension of the time of immobility (depression-like behavior). PD0325901 significantly reduced the decrease in PWL and the increased time of immobility after CCI. The decreased PWL and increased time of immobility were also reduced by 4-MC and by treatment with an ERK1/2 inhibitor. These effects of 4-MC i.c.v. were reversed by anti-BDNF and K252a. The analgesic effect of 4-MC i.c.v. was also antagonized by naloxone. Based on these results, we suggest that a lack of BDNF and activation of ERK1/2 in the pain-emotion network in the CNS may be involved in depression-like behavior during chronic pain. 4-MC i.c.v. ameliorates chronic pain and depression-like behavior by producing of BDNF and normalization of ERK1/2 activation. Therefore, enhancement of BDNF may be a new treatment strategy for chronic pain associated with depression. 相似文献
996.
997.
Itoh M Kuwahara J Itoh K Fukuda Yi Kohya M Shindo M Shishido K 《Bioorganic & medicinal chemistry letters》2002,12(16):2069-2072
Synthetic intermediates of alkaloid halichlorine with the azaspiro core structure have been found to induce apoptosis of cultured human cells including an acute monocytic leukemia cell line (THP-1) at micromolar concentrations. The novel biological activity of the intermediates was suggested to depend on the skeletal structure and silyloxymethyl functionality on the five-membered ring. 相似文献
998.
999.
We cloned MafG-2, a novel splice variant of MafG, from rat brain by RT-PCR method. MafG-2 differs from the previously published MafG by an insertion of 27 amino acids. Sequence analysis of the cDNA-encoded MafG-2 showed that MafG-2 contains basic domain and basic leucine zipper (bZip) motif. Transient transfection studies with GFP-MafG-2 chimera protein indicate that MafG-2 is localized in the nuclei of transfected COS-7 cells. To determine whether gene expression of mafG-2 mRNA is induced by an increase in extracellular protons, we analyzed expression of the mRNA in PC12 cells after an increase in extracellular proton concentration. We found that the mafG-2 mRNA expression increased when extracellular pH was decreased gradually from 7.40 to 7.20 and that there was a significant correlation between extracellular pH value and the expression of mafG-2 mRNA. These results suggest that an increase in extracellular proton may induce the expression of mafG-2 mRNA and MafG-2 may be involved in signal transduction of extracellular of H(+). 相似文献
1000.
Takayama K Ooto S Hangai M Arakawa N Oshima S Shibata N Hanebuchi M Inoue T Yoshimura N 《PloS one》2012,7(3):e33158