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951.
Antiproliferative effect of IL-1 is mediated by p38 mitogen-activated protein kinase in human melanoma cell A375. 总被引:6,自引:0,他引:6
S Itoh T Hattori H Hayashi Y Mizutani M Todo T Takii D Yang J C Lee S Matsufuji Y Murakami T Chiba K Onozaki 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(12):7434-7440
The role of p38 mitogen-activated protein kinase (MAPK) in IL-1-induced growth inhibition was investigated using IL-1-sensitive human melanoma A375-C2-1 cells and IL-1-resistant A375-R8 cells. In both cells, p38 MAPK was activated by IL-1. A selective inhibitor for p38 MAPK, SB203580, almost completely recovered the IL-1-induced growth inhibition in A375-C2-1 cells. IL-1-induced IL-6 production was also suppressed by SB203580. However, the reversal effect of SB203580 was not due to the suppression of IL-6 production because the SB203580 effect was still observed in the presence of exogenous IL-6. Down-regulation of ornithine decarboxylase (ODC) activity as well as its protein level has been shown to be essential for IL-1-induced growth inhibition. SB203580 also reversed the IL-1-induced down-regulation of ODC activity and intracellular polyamine levels without affecting ODC mRNA levels in A375-C2-1 cells. In IL-1-resistant R8 cells, however, IL-1 only slightly suppressed ODC activity. In A375-C2-1 cells, the mRNA expression level of antizyme (AZ), a regulatory factor of ODC activity, has been shown to be up-regulated by IL-1. IL-1-induced up-regulation of AZ mRNA level was not affected by SB203580. These findings demonstrate that p38 MAPK plays an important role in IL-1-induced growth inhibition in A375 cells through down-regulating ODC activity without affecting the level of ODC mRNA and AZ mRNA. In IL-1-resistant A375-R8 cells, IL-1 signaling pathway is deficient between p38 MAPK activation and down-regulation of ODC activity. 相似文献
952.
953.
Andrew M. Haidle Kaleen K. Childers Anna A. Zabierek Jason D. Katz James P. Jewell Yongquan Hou Michael D. Altman Alexander Szewczak Dapeng Chen Andreas Harsch Mansuo Hayashi Lee Warren Michael Hutton Hugh Nuthall Matt G. Stanton Ian W. Davies Ben Munoz Alan Northrup 《Bioorganic & medicinal chemistry letters》2017,27(1):109-113
Attempts to optimize pharmacokinetic properties in a promising series of pyrrolopyrimidinone MARK inhibitors for the treatment of Alzheimer’s disease are described. A focus on physical properties and ligand efficiency while prosecuting this series afforded key tool compounds that revealed a large discrepancy in the rat in vitro–in vivo DMPK (Drug Metabolism/Pharmacokinetics) correlation. These differences prompted an in vivo rat disposition study employing a radiolabeled representative of the series, and the results from this experiment justified the termination of any further optimization efforts. 相似文献
954.
955.
Variation in growth rate,carbon assimilation,and photosynthetic efficiency in response to nitrogen source and concentration in phytoplankton isolated from upper San Francisco Bay
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Gry Mine Berg Sara Driscoll Kendra Hayashi Melissa Ross Raphael Kudela 《Journal of phycology》2017,53(3):664-679
Six species of phytoplankton recently isolated from upper San Francisco Bay were tested for their sensitivity to growth inhibition by ammonium (NH4+), and for differences in growth rates according to inorganic nitrogen (N) growth source. The quantum yield of photosystem II (Fv/Fm) was a sensitive indicator of NH4+ toxicity, manifested by a suppression of Fv/Fm in a dose‐dependent manner. Two chlorophytes were the least sensitive to NH4+ inhibition, at concentrations of >3,000 μmoles NH4+ · L?1, followed by two estuarine diatoms that were sensitive at concentrations >1,000 μmoles NH4+ · L?1, followed lastly by two freshwater diatoms that were sensitive at concentrations between 200 and 500 μmoles NH4+ · L?1. At non‐inhibiting concentrations of NH4+, the freshwater diatom species grew fastest, followed by the estuarine diatoms, while the chlorophytes grew slowest. Variations in growth rates with N source did not follow taxonomic divisions. Of the two chlorophytes, one grew significantly faster on nitrate (NO3?), whereas the other grew significantly faster on NH4+. All four diatoms tested grew faster on NH4+ compared with NO3?. We showed that in cases where growth rates were faster on NH4+ than they were on NO3?, the difference was not larger for chlorophytes compared with diatoms. This holds true for comparisons across a number of culture investigations suggesting that diatoms as a group will not be at a competitive disadvantage under natural conditions when NH4+ dominates the total N pool and they will also not have a growth advantage when NO3? is dominant, as long as N concentrations are sufficient. 相似文献
956.
Xiaoyu Song Biao Zhou Lingyu Cui Di Lei Pingping Zhang Guodong Yao Mingyu Xia Toshihiko Hayashi Shunji Hattori Yuko Ushiki-Kaku Shin-ichi Tashiro Satoshi Onodera Takashi Ikejima 《Neurochemical research》2017,42(4):1073-1083
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aβ25-35-injected rats. Results demonstrated that silibinin significantly attenuated Aβ25-35-induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aβ25-35-injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ25-35-injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities. 相似文献
957.
958.
Mari Hikosaka Akihiko Murata Miya Yoshino Shin-Ichi Hayashi 《Biochemistry and Biophysics Reports》2017
Allergic conditions result in the increase of immunoglobulin (Ig)E-producing plasma cells (IgE-PCs); however, it is unclear how IgE production is qualitatively controlled. In this study, we found that IgE-PCs in spleen of immunized mice formed homotypic cell aggregates. By employing IgE-producing hybridomas (IgE-hybridomas) as a model of IgE-PCs, we showed that these cells formed aggregates in the presence of specific antigens (Ags). The formation of the Ag-induced cell aggregation involved secreted IgE and Fcγ receptor (FcγR)II/FcγRIII, but not FcεRs. Ag-induced cell aggregation plus lipopolysaccharide signaling resulted in an enhancement of IgE production in aggregated IgE-hybridomas. Furthermore, the administration of anti-FcγRII/FcγRIII antagonistic monoclonal antibody to immunized mice tended to reduce the splenic IgE-PC aggregation as well as the serum IgE levels. Taken together, our results suggested that Ag-IgE complexes induced IgE-PCs aggregation via FcγRII/FcγRIII, leading to the enhancement of IgE production. These findings suggest the presence of a novel mechanism for regulation of IgE production. 相似文献
959.
The production of recombinant protein in Escherichia coli is often hampered by low expression levels and low solubility. A variety of methodologies have been developed including protein production at low temperature, and fusion protein expression using soluble protein tags. Here, we present the novel cold-shock vector pCold-GST for high-level expression of soluble proteins in E. coli. This vector is a modified pCold I cold-shock vector that includes the glutathione S-transferase (GST) tag. The pCold-GST expression system developed was applied to 10 proteins that could not be expressed using conventional E. coli expression methodologies, and nine of these proteins were successfully obtained in the soluble fraction. The expression and purification of two unstable protein fragments were also demonstrated by employing a C-terminal hexa-histidine tag for purification purposes. The purified proteins were amenable to NMR analyses. These data suggest that the pCold-GST expression system can be utilized to improve the expression and purification of various proteins. 相似文献
960.
Molecular phylogeny and historical biogeography of the Holarctic wetland leaf beetle of the genus Plateumaris 总被引:1,自引:0,他引:1
Leaf beetles of the genus Plateumaris inhabit wetlands across the temperate zone of the Holarctic region. To explore the phylogeographic relationships among North American, East Asian, and European members of this genus and the origin of the species endemic to Japan, we studied the molecular phylogeny of 20 of the 27 species in this genus using partial sequences of mitochondrial cytochrome oxidase subunit I (COI) and the 16S and nuclear 28S rRNA genes. The molecular phylogeny revealed that three species endemic to Europe are monophyletic and sister to the remaining 11 North American and six Asian species. Within the latter clade, North American and Asian species did not show reciprocal monophyly. Dispersal-vicariance analysis and divergence time estimation revealed that the European and North America-Asian lineages diverged during the Eocene. Moreover, subsequent differentiation occurred repeatedly between North American and Asian species, which was facilitated by three dispersal events from North America to Asia and one in the opposite direction during the late Eocene through the late Miocene. Two Japanese endemics originated from different divergence events; one differentiated from the mainland lineage after differentiation from the North American lineage, whereas the other showed a deep coalescence from the North American lineage with no present-day sister species on the East Asian mainland. This study of extant insects provides molecular phylogenetic evidence for ancient vicariance between Europe and East Asia-North America, and for more recent (but pre-Pleistocene) faunal exchanges between East Asia and North America. 相似文献