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141.
142.
Takeshi Ishii Tomoe Yamada Taiki Mori Shigenori Kumazawa Koji Uchida Tsutomu Nakayama 《Free radical research》2013,47(11):1253-1260
Lipid peroxidation products contribute to protein aggregation that occurs during oxidative stress in a number of degenerative disorders. Acrolein (ACR), a highly toxic lipid peroxidation aldehyde, is a strong cross-linking agent of cellular components such as proteins. To understand the mechanisms of oxidative stress-induced protein aggregation, this study characterized the ACR modification of chain B from bovine insulin by mass spectrometry. To identify the cross-linking sites, the ACR-treated peptide was digested with a protease and the resulting peptides were analysed by liquid chromatography-tandem mass spectrometry. Inter- and intra-molecular cross-linking adducts were identified between amino groups and the side chain of histidine in the peptide. These results indicated that the ACR-induced cross-links were accompanied by two reactions, namely Michael addition and Schiff base formation. In conclusion, the use of mass spectrometric techniques provided chemical evidence for protein cross-linking with ACR. 相似文献
143.
Hiroshi Shiragami Yasuhiro Tanaka Yumiko Uchida Hisao Iwagami Kunisuke Izawa Toshihide Yukawa 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):391-400
Abstract Regioselective 2′-O-deacetylation of 9-(2,5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)adenine (1) is achieved by treatment of 1 with β-cyclodextrin (β-CyD) / aq. NaHCO3 or N2H4·H2O / EtOH. The 9-(5-O-Acetyl-3-bromo-3-deoxy-β-D-xylo-furanosyl)adenine (2) obtained is a common intermediate for the synthesis of 2′,3′-dideoxy-adenosine (ddA) (7) and 9-(2-fluoro-2,3-dideoxy-β-D-threo-pentofuranosyl)-adenine (F-ddA) (9). 相似文献
144.
Hiroshi Morioka Mikiko Kurihara Hiroyuki Kobayashi Kousuke Satou Yasuo Komatsu Makiyo Uchida 《Nucleosides, nucleotides & nucleic acids》2013,32(4-6):667-679
A monoclonal antibody (DEM-1) specific for the Dewar photoproduct is used for detection and quantification of photolesions in DNA. To help understand the molecular recognition of damaged DNA by the antibody protein, we have cloned and sequenced the variable region genes of DEM-1. We have also prepared Fab fragments of DEM-1 (DEM1Fab), and synthesized two kinds of 3′-biotinylated oligonucleotides of different lengths containing a central Dewar photoproduct of TpT to analyze the effects of the antigen size on the binding rates by means of surface plasmon resonance (SPR). Results obtained from SPR analyses suggest that DEM1Fab may recognize tetranucleotide unit as the epitope. 相似文献
145.
Florian Wilfling Huajin Wang Joel T. Haas Natalie Krahmer Travis J. Gould Aki Uchida Ji-Xin Cheng Morven Graham Romain Christiano Florian Fröhlich Xinran Liu Kimberly K. Buhman Rosalind A. Coleman Joerg Bewersdorf Robert V. Farese Tobias C. Walther 《Developmental cell》2013,24(4):384-399
Highlights? Triacylglyceride (TG) synthesis is coupled with lipid droplet (LD) growth ? Two LD populations exist: growing LDs, containing TG enzymes, and small LDs ? Specific TG synthesis enzymes move from the ER to LDs through membrane bridges ? LD localization of TG enzymes mediates expansion of a subset of LDs 相似文献
146.
Kentaro Uchida Kouji Naruse Masashi Satoh Kenji Onuma Masaki Ueno Shotaro Takano Ken Urabe Masashi Takaso 《Experimental Animals》2013,62(3):255-265
Although recent studies suggest that hyperlipidemia is a risk factor for osteoarthritis
(OA), the link between OA and hyperlipidemia is not fully understood. As the number of
activated, circulating myeloid cells is increased during hyperlipidemia, we speculate that
myeloid cells contribute to the pathology of OA. Here, we characterized myeloid cells in
STR/Ort mice, a murine osteoarthritis model, under hyperlipidemic conditions. Ratios of
myeloid cells in bone marrow, the spleen, and peripheral blood were determined by flow
cytometry. To examine the influence of the hematopoietic environment, including abnormal
stem cells, on the hematopoietic profile of STR/Ort mice, bone marrow transplantations
were performed. The relationship between hyperlipidemia and abnormal hematopoiesis was
examined by evaluating biochemical parameters and spleen weight of F2 animals
(STR/Ort x C57BL/6J). In STR/Ort mice, the ratio of CD11b+Gr1+ cells
in spleens and peripheral blood was increased, and CD11b+Gr1+ cells
were also present in synovial tissue. Splenomegaly was observed and correlated with the
ratio of CD11b+Gr1+ cells. When bone marrow from GFP-expressing mice
was transplanted into STR/Ort mice, no difference in the percentage of
CD11b+Gr1+ cells was observed between transplanted and age-matched
STR/Ort mice. Analysis of biochemical parameters in F2 mice showed that spleen
weight correlated with serum total cholesterol. These results suggest that the increase in
circulating and splenic CD11b+Gr1+ cells in STR/Ort mice originates
from hypercholesterolemia. Further investigation of the function of
CD11b+Gr1+ cells in synovial tissue may reveal the pathology of OA
in STR/Ort mice. 相似文献
147.
148.
Tomoyuki Yamanaka Asako Tosaki Masaru Kurosawa Kazunori Akimoto Tomonori Hirose Shigeo Ohno Nobutaka Hattori Nobuyuki Nukina 《PloS one》2013,8(12)
Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS). Recent studies have established the significance of atypical protein kinase C (aPKC) and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation. 相似文献
149.
Yoji Kukita Junji Uchida Shigeyuki Oba Kazumi Nishino Toru Kumagai Kazuya Taniguchi Takako Okuyama Fumio Imamura Kikuya Kato 《PloS one》2013,8(11)
The detection of rare mutants using next generation sequencing has considerable potential for diagnostic applications. Detecting circulating tumor DNA is the foremost application of this approach. The major obstacle to its use is the high read error rate of next-generation sequencers. Rather than increasing the accuracy of final sequences, we detected rare mutations using a semiconductor sequencer and a set of anomaly detection criteria based on a statistical model of the read error rate at each error position. Statistical models were deduced from sequence data from normal samples. We detected epidermal growth factor receptor (EGFR) mutations in the plasma DNA of lung cancer patients. Single-pass deep sequencing (>100,000 reads) was able to detect one activating mutant allele in 10,000 normal alleles. We confirmed the method using 22 prospective and 155 retrospective samples, mostly consisting of DNA purified from plasma. A temporal analysis suggested potential applications for disease management and for therapeutic decision making to select epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). 相似文献
150.
Miho Chikazawa Natsuki Otaki Takahiro Shibata Takehiko Yasueda Tsukasa Matsuda Koji Uchida 《PloS one》2013,8(7)
Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and enhances the engulfment of apoptotic cells by macrophages. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in the MFG-E8-deficient (MFG-E8−/−) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus. We found that the MFG-E8 deficiency was accompanied by the increased production of immunoglobulins. Further Western blot and ELISA analyses validated the increase in the IgM levels in the MFG-E8−/− mice. It was also revealed that the sera from the MFG-E8−/− mice cross-reacted with oxidation-specific epitopes generated upon incubation of serum albumin with the peroxidized lipids. Among the modified proteins with several unsaturated aldehydes of chain lengths varying from three to nine carbons, the MFG-E8−/− mice sera exclusively cross-reacted with the protein-bound 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of ω6 polyunsaturated fatty acids. In addition, the IgM monoclonal antibodies (mAbs) that selectively cross-reacted with the ONE-modified proteins were generated from the MFG-E8−/− mice. A subset of the ONE-specific IgM mAbs significantly recognized the late apoptotic and necrotic cells and enhanced the phagocytosis by macrophages. These data demonstrate that the impairment of the phagocytic clearance of apoptotic cells through MFG-E8 can lead to the generation of natural antibodies, which may play a critical role in removing multiple damage-associated molecules, including oxidation-specific epitopes and late apoptotic/necrotic cells. 相似文献