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31.
Kazuhiro Shiozaki Kazuki Takeshita Mako Ikeda Asami Ikeda Yusuke Harasaki Masaharu Komatsu Shoji Yamada Kazunori Yamaguchi Taeko Miyagi 《Biochimie》2013
Mammalian Neu3 sialidases are involved in various biological processes, such as cell death and differentiation, through desialylation of gangliosides. The enzymatic profile of Neu3 seems to be highly conserved from birds to mammals. In fish, the functional properties of Neu3 sialidase are not clearly understood, with the partial exception of the zebrafish form. To cast further light on the molecular evolution of Neu3 sialidase, we identified the encoding genes in the medaka Oryzias latipes and investigated the properties of the enzyme. PCR amplification using medaka brain cDNA allowed identification of two novel medaka Neu3 genes, neu3a and neu3b. The YRIP, VGPG motif and Asp-Box, characteristic of consensus motifs of sialidases, were well conserved in the both medaka Neu3 sialidases. When each gene was transfected into HEK293 to allow cell lysates for the use of enzymatic characterization, two Neu3 sialidases showed strict substrate specificity toward gangliosides, similar to mammalian Neu3. The optimal pH values were at pH 4.2 and pH 4.0, respectively, and neu3b in particular showed a broad optimum. Immunofluorescence assays indicated neu3a localization at plasma membranes, while neu3b was found in cytosol. The tissue distribution of two genes was then investigated by estimation of mRNA expression and sialidase activity, both being dominantly expressed in the brain. In neu3a gene-transfected neuroblastoma cells, the enzyme was found to positively regulate retinoic acid-induced differentiation with the elongation of axon length. On the other hand, neu3b did not affect neurite formation. These results and phylogenetic analysis suggested that the medaka neu3a is an evolutionally conserved sialidase with regard to enzymatic properties, whereas neu3b is likely to have originally evolved in medaka. 相似文献
32.
33.
Fumiaki Nakayama Sachiko Umeda Tomomi Ichimiya Shin Kamiyama Masaharu Hazawa Takeshi Yasuda Shoko Nishihara Takashi Imai 《FEBS letters》2013,587(2):231-237
This study focuses on clarifying the contribution of sulfation to radiation-induced apoptosis in human Burkitt’s lymphoma cell lines, using 3′-phosphoadenosine 5′-phosphosulfate transporters (PAPSTs). Overexpression of PAPST1 or PAPST2 reduced radiation-induced apoptosis in Namalwa cells, whereas the repression of PAPST1 expression enhanced apoptosis. Inhibition of PAPST slightly decreased keratan sulfate (KS) expression, so that depletion of KS significantly increased radiation-induced apoptosis. In addition, the repression of all three N-acetylglucosamine-6-O-sulfotransferases (CHST2, CHST6, and CHST7) increased apoptosis. In contrast, PAPST1 expression promoted the phosphorylation of p38 MAPK and Akt in irradiated Namalwa cells. These findings suggest that 6-O-sulfation of GlcNAc residues in KS reduces radiation-induced apoptosis of human Burkitt’s lymphoma cells. 相似文献
34.
Salinization of crop fields is a pressing matter for sustainable agriculture under desertification and is largely attributed to root absorptive functions of the major crops such as maize. The rates of water and ion absorption of intact root system of maize plants were measured under the salinized condition, and the salt absorptive function of maize roots was analyzed by applying different two kinetic models of root ion absorption (i.e. the concentration dependent model and the transpiration integrated model). The absorption rates for salinization ions (Na+, Cl?, Ca2+ and Mg2+) were found to depend on ion mass flow through roots driven by the transpiration, and therefore the transpiration integrated model represented more accurately rates of root ion absorption. The root absorption of salinization ions was characterized quantitatively by two model parameters of Q′max and K′M involved in the transpiration integrated model, which are considered to relate to the potential absorbing power and the ion affinity of transport proteins on root cell membranes, respectively. 相似文献
35.
Keisuke Maruyama Masaharu Nakamura Shusuke Tomoshige Kazuyuki Sugita Makoto Makishima Yuichi Hashimoto Minoru Ishikawa 《Bioorganic & medicinal chemistry letters》2013,23(14):4031-4036
Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ERα/ERβ subtype selectivity. Among the compounds examined, 18 was found to be a potent ERα-antagonist with high selectivity over ERβ and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ERα. ERα-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. 相似文献
36.
Norio Kurihara Yuzuru Sanemitsu Tomio Kimura Masaharu Kobayashi Minoru Nakajima Yoshiyuki Tamura 《Bioscience, biotechnology, and biochemistry》2013,77(5):784-797
β-BTC(3, 4/5, 6),1) γ-BTC(3, 4, 6/5), and ε-BTC(3, 4, 5/6) were synthesized from α-BTC (3, 6/4, 5) by stepwise routes. 相似文献
37.
Kazuaki Manabe Mitsuyoshi Morii Masaru Honjo Masaharu Ohoka Kouichiro Fushimi Akiko Sawakura 《Bioscience, biotechnology, and biochemistry》2013,77(8):2261-2267
Bacillus subtilis 1A20 transformed with a hybrid plasmid, pNP150, to which a DNA fragment from Bacillus amyloliquefaciens F was attached, produced a large amount of a neutral protease. To identify the origin of the gene specifying this neutral protease, neutral proteases from B. amyloliquefaciens F, B. subtilis NP58 (a derivative of Marburg 6160), and B. subtilis 1A20 transformed with pNP150 were purified. We investigated their immunological properties and primary structures.The proteases from these two species were indistinguishable by chromatography, but they were distinguishable from each other by SDS-polyacrylamide gel electrophoresis and double immunodiffusion. Amino acid sequencing of these two proteases by Edman degradation showed that there were four substitutions in the 20-residue amino acid sequence from the N-termini.Neutral protease from the transformant had the same immunological characteristics and N-terminal amino acid sequence as that from B. amyloliquefaciens. These results meant that the gene in question was derived from a gene specifying the neutral protease in this bacterium. 相似文献
38.
Oxalacetate carboxylyase was extracted from pig heart muscle and purified about 40 fold by means of acid and heat treatments, salting out and three steps of column chromatography. Some properties of the enzyme were studied by manometric and spectrophotometric measurements. The enzyme activity was optimal at pH 7. Km for oxalacetate was 4.3 × 10?3 m/liter and the activation energy of the enzyme reaction was 15 kcal/m. The enzyme was activated by certain bivalent cations, among which Mn2+ was the most effective. Cu2+, Hg2+, some metal chelating reagents (EDTA, citrate and Oxalate) and pCMB strongly inhibited the enzyme activity. Inhibition by avidin was not observed, suggesting that biotin was not involved in the reaction as the prosthetic group of the enzyme. 相似文献
39.
Huifang Hao Yutaka Maeda Takuya Fukazawa Tomoki Yamatsuji Munenori Takaoka Xiao-Hong Bao Junji Matsuoka Tatsuo Okui Tsuyoshi Shimo Nagio Takigawa Yasuko Tomono Motowo Nakajima Iris M. Fink-Baldauf Sandra Nelson William Seibel Ruben Papoian Jeffrey A. Whitsett Yoshio Naomoto 《PloS one》2013,8(8)
Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. MDK activates the PI3K pathway and induces anti-apoptotic activity, in turn enhancing the survival of tumors. Therefore, the inhibition of MDK is considered a potential strategy for cancer therapy. In the present study, we demonstrate a novel small molecule compound (iMDK) that targets MDK. iMDK inhibited the cell growth of MDK-positive H441 lung adenocarcinoma cells that harbor an oncogenic KRAS mutation and H520 squamous cell lung cancer cells, both of which are types of untreatable lung cancer. However, iMDK did not reduce the cell viability of MDK-negative A549 lung adenocarcinoma cells or normal human lung fibroblast (NHLF) cells indicating its specificity. iMDK suppressed the endogenous expression of MDK but not that of other growth factors such as PTN or VEGF. iMDK suppressed the growth of H441 cells by inhibiting the PI3K pathway and inducing apoptosis. Systemic administration of iMDK significantly inhibited tumor growth in a xenograft mouse model in vivo. Inhibition of MDK with iMDK provides a potential therapeutic approach for the treatment of lung cancers that are driven by MDK. 相似文献
40.
Taku Watanabe Ichizo Tsujino Satoshi Konno Yoichi M. Ito Chisa Takashina Takahiro Sato Akira Isada Hiroshi Ohira Yoshinori Ohtsuka Yuma Fukutomi Hiroyuki Nakamura Yukio Kawagishi Chiharu Okada Nobuyuki Hizawa Masami Taniguchi Akira Akasawa Masaharu Nishimura 《PloS one》2016,11(3)