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991.
Yusuke Goto Rika Nishikawa Satoko Kojima Takeshi Chiyomaru Hideki Enokida Satoru Inoguchi Takashi Kinoshita Miki Fuse Shinichi Sakamoto Masayuki Nakagawa Yukio Naya Tomohiko Ichikawa Naohiko Seki 《FEBS letters》2014
Our recent study of the microRNA expression signature of prostate cancer (PCa) revealed that microRNA-224 (miR-224) is significantly downregulated in PCa tissues. Here, we found that restoration of miR-224 significantly inhibits PCa cell migration and invasion. Additionally, we found that oncogenic TPD52 is a direct target of miR-224 regulation. Silencing of the TPD52 gene significantly inhibits cancer cell migration and invasion. Moreover, TPD52 expression is upregulated in cancer tissues and negatively correlates with miR-224 expression. We conclude that loss of tumour-suppressive miR-224 enhances cancer cell migration and invasion in PCa through direct regulation of oncogenic TPD52. 相似文献
992.
Nobutaka Matsumura Mako Takami Masayasu Okochi Satoko Wada-Kakuda Hitomi Fujiwara Shinji Tagami Satoru Funamoto Yasuo Ihara Maho Morishima-Kawashima 《The Journal of biological chemistry》2014,289(8):5109-5121
γ-Secretase generates amyloid β-protein (Aβ), a pathogenic molecule in Alzheimer disease, through the intramembrane cleavage of the β-carboxyl-terminal fragment (βCTF) of β-amyloid precursor protein. We previously showed the framework of the γ-secretase cleavage, i.e. the stepwise successive processing of βCTF at every three (or four) amino acids. However, the membrane integrity of γ-secretase was not taken into consideration because of the use of the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonic acid-solubilized reconstituted γ-secretase system. Here, we sought to address how the membrane-integrated γ-secretase cleaves βCTF by using γ-secretase associated with lipid rafts. Quantitative analyses using liquid chromatography-tandem mass spectrometry of the βCTF transmembrane domain-derived peptides released along with Aβ generation revealed that the raft-associated γ-secretase cleaves βCTF in a stepwise sequential manner, but novel penta- and hexapeptides as well as tri- and tetrapeptides are released. The cropping of these peptides links the two major tripeptide-cleaving pathways generating Aβ40 and Aβ42 at several points, implying that there are multiple interactive pathways for the stepwise cleavages of βCTF. It should be noted that Aβ38 and Aβ43 are generated through three routes, and γ-secretase modulator 1 enhances all the three routes generating Aβ38, which results in decreases in Aβ42 and Aβ43 and an increase in Aβ38. These observations indicate that multiple interactive pathways for stepwise successive processing by γ-secretase define the species and quantity of Aβ produced. 相似文献
993.
Eriko Yamamoto Toyoyoshi Uchida Hiroko Abe Hikari Taka Tsutomu Fujimura Koji Komiya Akemi Hara Takeshi Ogihara Yoshio Fujitani Takashi Ueno Satoru Takeda Hirotaka Watada 《Biochemical and biophysical research communications》2014
Autophagy is a tightly regulated self-digestion system. As in other cell types, autophagy plays an essential role in the homeostasis of pancreatic beta cells. However, the mechanisms involved in the deterioration of beta cell function caused by autophagic failure have not yet been fully elucidated. To gain insight into its mechanisms, we compared the protein expression of islets from beta cell-specific Atg7-deficient mice (Atg7Δβ-cell mice) and their controls (Atg7f/f mice). Liquid chromatography/mass spectrometry after 1-dimensional electrophoresis identified the increased expression of ERp57/GRP58 in islets isolated from Atg7Δβ-cell mice compared with those from Atg7f/f mice. The expression level of ERp57 was also elevated in rat insulinoma INS-1 cells by inducible knock-down of the atg7-gene. In Atg7 knock-down INS-1 cells, the suppression of ERp57 expression by siRNA resulted in an increase in the level of cleaved Caspase-3 protein and a decrease in the number of live cells. Furthermore, cell cycle analyses demonstrated that the suppressed expression of ERp57 increased the sub-G1 population. These data reveal that increased expression of ERp57 may contribute to the protection from beta cell death caused by autophagic failure. 相似文献
994.
995.
Phytoplankton in the mixed layer is exposed to increasing levels of light when transported to the surface layer of the ocean. The photoprotective response of natural assemblages of phytoplankton can differ among community structures. We investigated photoprotective acclimation and xanthophyll cycle pigments in size-fractionated natural phytoplankton assemblages during the austral summer in the Indian sector of the Southern Ocean. We estimated concentrations of phytoplankton pigments in the micro-size fractions (>20 μm) and nano-size fractions (2–20 μm) by subtracting concentrations in the <20 μm fractions from concentrations in the bulk samples, and by subtracting concentrations in the <2 μm fractions from concentrations in the <20 μm fractions, respectively. Changes in the ratios of the xanthophyll cycle pigments diadinoxanthin (DD) and diatoxanthin (DT) were determined at three optical depths in the mixed layer and during 48 h deck incubations under solar photosynthetically available radiation and ultraviolet radiation. Large variations in (DD + DT)/Chl a in the mixed layer (percent coefficient of variation >67 %) and in deck incubation bottles under variable light conditions (>75 % of the temporal variation) for the micro-size fractions suggest a higher potential for photoprotective acclimation than for the nano-size fractions. Decreases in DT/(DD + DT) with increases in the optical depth of the mixed layer (ζ MLD) suggest that larger variations in light availability in the mixed layer might predict lower values of DT/(DD + DT) at the surface, regardless of cell size. 相似文献
996.
Bo Yin Dongbing Cui Lujia Zhang Shuiqin Jiang Satoru Machida Y. Adam Yuan Dongzhi Wei 《Proteins》2014,82(11):2925-2935
Gox2253 from Gluconobacter oxydans belongs to the short‐chain dehydrogenases/reductases family, and catalyzes the reduction of heptanal, octanal, nonanal, and decanal with NADPH. To develop a robust working platform to engineer novel G. oxydans oxidoreductases with designed coenzyme preference, we adopted a structure based rational design strategy using computational predictions that considers the number of hydrogen bonds formed between enzyme and docked coenzyme. We report the crystal structure of Gox2253 at 2.6 Å resolution, ternary models of Gox2253 mutants in complex with NADH/short‐chain aldehydes, and propose a structural mechanism of substrate selection. Molecular dynamics simulation shows that hydrogen bonds could form between 2′‐hydroxyl group in the adenosine moiety of NADH and the side chain of Gox2253 mutant after arginine at position 42 is replaced with tyrosine or lysine. Consistent with the molecular dynamics prediction, Gox2253‐R42Y/K mutants can use both NADH and NADPH as a coenzyme. Hence, the strategies here could provide a practical platform to engineer coenzyme selectivity for any given oxidoreductase and could serve as an additional consideration to engineer substrate‐binding pockets. Proteins 2014; 82:2925–2935. © 2014 Wiley Periodicals, Inc. 相似文献
997.
Mina Sasaki Hiroshi Kajiya Satoru Ozeki Koji Okabe Tetsuro Ikebe 《Biochemical and biophysical research communications》2014
Reactive oxygen species (ROS) can cause severe damage to DNA, proteins and lipids in normal cells, contributing to carcinogenesis and various pathological conditions. While cellular senescence arrests the early phase of cell cycle without any detectable telomere loss or dysfunction. ROS is reported to contribute to induction of cellular senescence, as evidence by its premature onset upon treatment with antioxidants or inhibitors of cellular oxidant scavengers. Although cellular senescence is known to be implicated in tumor suppression, it remains unknown whether ROS initially contributed to be cellular senescence in normal human epidermal keratinocytes (NHEK) and their malignant counterparts. To clarify whether ROS induce cellular senescence in NHEKs, we examined the effect of hydrogen peroxide (H2O2) on the expression of cellular senescence-associated molecules in NHEKs, compared to in squamous carcinoma cells (SCCs). Hydrogen peroxide increased the number of cells positive in senescence associated-β-galactosidase (SA-β-Gal) activity in NHEKs, but not SCCs. The expression of cyclin-dependent kinase (CDK) inhibitors, especially p16INK4a was upregulated in NHEKs treated with H2O2. Interestingly, H2O2 suppressed the methylation of p16INK4a, promoter region in NHEKs, but not in SCCs. Hydrogen peroxide also suppressed the expression of phosphorylated Rb and CDK4, resulting in arrest in G0/G1 phase in NHEKs, but not SCCs. 相似文献
998.
Saurabh Sahar Satoru Masubuchi Kristin Eckel-Mahan Simone Vollmer Luisa Galla Nicholas Ceglia Selma Masri Teresa K. Barth Benedetto Grimaldi Opeyemi Oluyemi Giuseppe Astarita William C. Hallows Daniele Piomelli Axel Imhof Pierre Baldi John M. Denu Paolo Sassone-Corsi 《The Journal of biological chemistry》2014,289(9):6091-6097
999.
Kaoru Kuriiwa Satoru N. Chiba Hiroyuki Motomura Keiichi Matsuura 《Ichthyological Research》2014,61(4):361-374
To investigate the influence of the Kuroshio Current on the high diversity of marine fishes in Japanese waters, the intraspecific phylogeographic structure of Blacktip Grouper, Epinephelus fasciatus, was determined. The genetic analysis of E. fasciatus indicated three intraspecific mtDNA lineages representing different evolutionary histories: the first lineage differentiated in Japanese waters during a long period of fluctuations of the ancient Kuroshio Current, the second lineage, widely distributed in the tropical western Pacific, was transported to Japanese waters by the Kuroshio Current and the third lineage was distributed primarily around the Ogasawara (Bonin) Islands. Present-day sympatric distributions of the three lineages, characterized by different ratios of such individuals at each geographic site, indicated a complex genetic pattern that was classified into three demographic groups, the dispersal and gene flows of which were strongly influenced by the Kuroshio Current and factors such as countercurrent and island arc. Genetic breaks in E. fasciatus populations were congruent with other fish faunal boundaries in Japanese waters. 相似文献
1000.
Yoshikazu Hasegawa Yoko Daitoku Seiya Mizuno Yoko Tanimoto Saori Mizuno-Iijima Miki Matsuo Noriko Kajiwara Masatsugu Ema Hisashi Oishi Yoshihiro Miwa Kazuyuki Mekada Atsushi Yoshiki Satoru Takahashi Fumihiro Sugiyama Ken-ichi Yagami 《Experimental Animals》2014,63(2):183-191
Cre/loxP system-mediated site-specific recombination is utilized to study gene function
in vivo. Successful conditional knockout of genes of interest is
dependent on the availability of Cre-driver mice. We produced and characterized pancreatic
β cell-specific Cre-driver mice for use in diabetes mellitus research. The gene encoding
Cre was inserted into the second exon of mouse Ins1 in a bacterial
artificial chromosome (BAC). Five founder mice were produced by microinjection of
linearized BAC Ins1-cre. The transgene was integrated between
Mafa and the telomere on chromosome 15 in one of the founders, BAC
Ins1-cre25. To investigate Cre-loxP recombination, BAC Ins1-cre25 males were crossed with
two different Cre-reporters, R26R and R26GRR females. On gross observation, reporter
signal after Cre-loxP recombination was detected exclusively in the adult pancreatic
islets in both F1 mice. Immunohistological analysis indicated that Cre-loxP
recombination-mediated reporter signal was colocalized with insulin in pancreatic islet
cells of both F1 mice, but not with glucagon. Moreover, Cre-loxP recombination
signal was already observed in the pancreatic islets at E13.5 in both F1
fetuses. Finally, we investigated ectopic Cre-loxP recombination for
Ins1, because the ortholog Ins2 is also expressed in the
brain, in addition to the pancreas. However, there was no Cre-loxP recombination-mediated
reporter signal in the brain of both F1 mice. Our data suggest that BAC
Ins1-cre25 mice are a useful Cre-driver C57BL/6N for pancreatic β cell-specific Cre-loxP
recombination, except for crossing with knock-in mice carrying floxed gene on chromosome
15. 相似文献