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71.
Hirano K Matsui H Tanaka T Matsuura F Satouchi K Koike T 《Journal of biochemistry》2004,136(4):477-483
1,2-Didocosahexaenoyl phosphatidylcholine (PC), which has highly unsaturated fatty acid at both sn-1 and sn-2 positions of glycerol, is a characteristic molecular species of bonito muscle. To examine the involvement of a de novo route in its synthesis, the molecular species of phosphatidic acid (PA) were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a 1,3-bis[bis(pyridin-2-ylmethyl)amino]propan-2-olato dizinc(II) complex, a novel phosphate-capture molecule. However, 1,2-didocosahexaenoyl species could not be detected. Next, 1,2-didocosahexaenoyl PC synthesis by the cytosolic lysophosphatidylcholine (LPC)/transacylase was examined using endogenous LPC from bonito muscle, in which the 2-docosahexaenoyl species is abundant. The LPC/transacylase synthesized 1,2-didocosahexaenoyl PC as the most abundant molecular species. For further characterization, the LPC/transacylase was purified to homogeneity from the 100,000 x g supernatant of bonito muscle. The isolated LPC/transacylase is a labile glycoprotein with molecular mass of 52 kDa including a 5-kDa sugar moiety. The LPC/transacylase showed a PC synthesis (transacylase activity) below and above the critical micelle concentration of substrate LPC, and fatty acid release (lysophospholipase activity) was always smaller than the transacylase activity, even with a monomeric substrate. These results suggest that the LPC/transacylase is responsible for the synthesis of 1,2-didocosahexaenoyl PC. 相似文献
72.
Prentice E Jerome WG Yoshimori T Mizushima N Denison MR 《The Journal of biological chemistry》2004,279(11):10136-10141
The coronavirus mouse hepatitis virus (MHV) performs RNA replication on double membrane vesicles (DMVs) in the cytoplasm of the host cell. However, the mechanism by which these DMVs form has not been determined. Using genetic, biochemical, and cell imaging approaches, the role of autophagy in DMV formation and MHV replication was investigated. The results demonstrated that replication complexes co-localize with the autophagy proteins, microtubule-associated protein light-chain 3 and Apg12. MHV infection induces autophagy by a mechanism that is resistant to 3-methyladenine inhibition. MHV replication is impaired in autophagy knockout, APG5-/-, embryonic stem cell lines, but wild-type levels of MHV replication are restored by expression of Apg5 in the APG5-/-cells. In MHV-infected APG5-/-cells, DMVs were not detected; rather, the rough endoplasmic reticulum was dramatically swollen. The results of this study suggest that autophagy is required for formation of double membrane-bound MHV replication complexes and that DMV formation significantly enhances the efficiency of replication. Furthermore, the rough endoplasmic reticulum is implicated as the possible source of membranes for replication complexes. 相似文献
73.
Miyajima Y Nakamura H Kuwata Y Lee JD Masunaga S Ono K Maruyama K 《Bioconjugate chemistry》2006,17(5):1314-1320
The nido-carborane lipid 2 as a double-tailed boron lipid was synthesized from heptadecanol in five steps. The lipid 2 formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf(+)-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO(2)H moieties of Tf(-)-PEG-CL liposomes. The biodistribution of Tf(+)-PEG-CL liposomes, in which (125)I-tyraminyl inulins were encapsulated, showed that Tf(+)-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor/blood concentration ratio, although Tf(-)-PEG-CL liposomes were gradually released from tumor tissues with time. A boron concentration of 22 ppm in tumor tissues was achieved by the injection of Tf(+)-PEG-CL liposomes at 7.2 mg/kg body weight boron in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf(+)-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf(+)-PEG-CL liposomes; one of them even survived for 52 days after BNCT. 相似文献
74.
ALIS are stress-induced protein storage compartments for substrates of the proteasome and autophagy 总被引:1,自引:0,他引:1
Szeto J Kaniuk NA Canadien V Nisman R Mizushima N Yoshimori T Bazett-Jones DP Brumell JH 《Autophagy》2006,2(3):189-199
Misfolded proteins can be directed into cytoplasmic aggregates such as aggresomes and dendritic cell aggresome-like induced structures (DALIS). DALIS were originally identified in lipopolysaccharide-stimulated dendritic cells and act as storage compartments for polyubiquitinated Defective Ribosomal Products (DRiPs) prior to their clearance by the proteasome. Here we demonstrate that ubiquitinated protein aggregates that are similar to DALIS, and not related to aggresomes, can be observed in several cell types in response to stress, including oxidative stress, transfection, and starvation. Significantly, both immune and nonimmune cells could form these aggresome-like induced structures (ALIS). Protein synthesis was essential for ALIS formation in response to oxidative stress, indicating that DRiP formation was required. Furthermore, puromycin, which increases DRiP formation, was sufficient to induce ALIS formation. Inhibition of either proteasomes or of autophagy interfered with ALIS clearance in puromycin treated cells. Autophagy inhibition enhanced ALIS formation under a variety of stress conditions. During starvation, ALIS formation in autophagy-deficient cells was only partially inhibited by protein synthesis inhibitors, indicating that both long-lived proteins and DRiPs can be targeted to ALIS. Together, these findings demonstrate that ALIS act as generalized stress-induced protein storage compartments for substrates of the proteasome and autophagy. 相似文献
75.
Emiko Yoda Keiko Hachisu Yoshitaka Taketomi Kotomi Yoshida Masanori Nakamura Kazutaka Ikeda Ryo Taguchi Yoshihito Nakatani Hiroshi Kuwata Makoto Murakami Ichiro Kudo Shuntaro Hara 《Journal of lipid research》2010,51(10):3003-3015
Group VIB Ca2+-independent phospholipase A2γ (iPLA2γ) is a membrane-bound iPLA2 enzyme with unique features, such as the utilization of distinct translation initiation sites and the presence of mitochondrial and peroxisomal localization signals. Here we investigated the physiological functions of iPLA2γ by disrupting its gene in mice. iPLA2γ-knockout (KO) mice were born with an expected Mendelian ratio and appeared normal and healthy at the age of one month but began to show growth retardation from the age of two months as well as kyphosis and significant muscle weakness at the age of four months. Electron microscopy revealed swelling and reduced numbers of mitochondria and atrophy of myofilaments in iPLA2γ-KO skeletal muscles. Increased lipid peroxidation and the induction of several oxidative stress-related genes were also found in the iPLA2γ-KO muscles. These results provide evidence that impairment of iPLA2γ causes mitochondrial dysfunction and increased oxidative stress, leading to the loss of skeletal muscle structure and function. We further found that the compositions of cardiolipin and other phospholipid subclasses were altered and that the levels of myoprotective prostanoids were reduced in iPLA2γ-KO skeletal muscle. Thus, in addition to maintenance of homeostasis of the mitochondrial membrane, iPLA2γ may contribute to modulation of lipid mediator production in vivo. 相似文献
76.
Koga R Hamano S Kuwata H Atarashi K Ogawa M Hisaeda H Yamamoto M Akira S Himeno K Matsumoto M Takeda K 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(10):7059-7066
Host resistance to the intracellular protozoan parasite Trypanosoma cruzi depends on IFN-gamma production by T cells and NK cells. However, the involvement of innate immunity in host resistance to T. cruzi remains unclear. In the present study, we investigated host defense against T. cruzi by focusing on innate immunity. Macrophages and dendritic cells (DCs) from MyD88(-/-)TRIF(-/-) mice, in which TLR-dependent activation of innate immunity was abolished, were defective in the clearance of T. cruzi and showed impaired induction of IFN-beta during T. cruzi infection. Neutralization of IFN-beta in MyD88(-/-) macrophages led to enhanced T. cruzi growth. Cells from MyD88(-/-)IFNAR1(-/-) mice also showed impaired T. cruzi clearance. Furthermore, both MyD88(-/-)TRIF(-/-) and MyD88(-/-)IFNAR1(-/-) mice were highly susceptible to in vivo T. cruzi infection, highlighting the involvement of innate immune responses in T. cruzi infection. We further analyzed the molecular mechanisms for the IFN-beta-mediated antitrypanosomal innate immune responses. MyD88(-/-)TRIF(-/-) and MyD88(-/-)IFNAR1(-/-) macrophages and DCs exhibited defective induction of the GTPase IFN-inducible p47 (IRG47) after T. cruzi infection. RNA interference-mediated reduction of IRG47 expression in MyD88(-/-) macrophages resulted in increased intracellular growth of T. cruzi. These findings suggest that TLR-dependent expression of IFN-beta is involved in resistance to T. cruzi infection through the induction of IRG47. 相似文献
77.
Mohamed-Elamir F. Hegazy Chika Kuwata Akihito Matsushima Ahmed A. Ahmed Toshifumi Hirata 《Journal of Molecular Catalysis .B, Enzymatic》2006,39(1-4):13
The biotransformation of sesquiterpenoids having an α,β-unsaturated carbonyl group, such as α-santonin (1), lancerodiol p-hydroxybenzoate (2), 8,9-dehydronootkatone (3), and nootkatone (4), with cultured suspension cells of Marchantia polymorpha was investigated. It was found that the CC double bond of 1 and 2 was hydrogenated to give 1,2-dihydro-α-santonin (5) and 3,4-dihydrolancerodiol p-hydroxybenzoate (6), respectively, while the allylic position of the CC double bond of 3 and 4 was hydroxylated to give 13-hydroxy-8,9-dehydronootkatone (7) and 9-hydroxynootkatone (8), respectively. 相似文献
78.
Wu F Ourmanov I Kuwata T Goeken R Brown CR Buckler-White A Iyengar R Plishka R Aoki ST Hirsch VM 《Journal of virology》2012,86(16):8835-8847
Simian immunodeficiency virus (SIV) infection of rhesus macaques has become an important surrogate model for evaluating HIV vaccine strategies. The extreme resistance to neutralizing antibody (NAb) of many commonly used strains, such as SIVmac251/239 and SIVsmE543-3, limits their potential relevance for evaluating the role of NAb in vaccine protection. In contrast, SIVsmE660 is an uncloned virus that appears to be more sensitive to neutralizing antibody. To evaluate the role of NAb in this model, we generated full-length neutralization-sensitive molecular clones of SIVsmE660 and evaluated two of these by intravenous inoculation of rhesus macaques. All animals became infected and maintained persistent viremia that was accompanied by a decline in memory CD4(+) T cells in blood and bronchoalveolar lavage fluid. High titers of autologous NAb developed by 4 weeks postinoculation but were not associated with control of viremia, and neutralization escape variants were detected concurrently with the generation of NAb. Neutralization escape was associated with substitutions and insertion/deletion polymorphisms in the V1 and V4 domains of envelope. Analysis of representative variants revealed that escape variants also induced NAbs within a few weeks of their appearance in plasma, in a pattern that is reminiscent of the escape of human immunodeficiency virus type 1 (HIV-1) isolates in humans. Although early variants maintained a neutralization-sensitive phenotype, viruses obtained later in infection were significantly less sensitive to neutralization than the parental viruses. These results indicate that NAbs exert selective pressure that drives the evolution of the SIV envelope and that this model will be useful for evaluating the role of NAb in vaccine-mediated protection. 相似文献
79.
Satoshi N. Suzuki Masae I. Ishihara Masahiro Nakamura Shin Abe Tsutom Hiura Kosuke Homma Motoki Higa Daisuke Hoshino Kazuhiko Hoshizaki Hideyuki Ida Ken Ishida Motohiro Kawanishi Kazutaka Kobayashi Koichiro Kuraji Shigeo Kuramoto Takashi Masaki Kaoru Niiyama Mahoko Noguchi Haruto Nomiya Satoshi Saito Takeshi Sakai Michinori Sakimoto Hitoshi Sakio Tamotsu Sato Hirofumi Shibano Mitsue Shibata Maki Suzuki Atsushi Takashima Hiroshi Tanaka Masahiro Takagi Naoaki Tashiro Naoko Tokuchi Toshiya Yoshida Yumiko Yoshida 《Ecological Research》2012,27(6):989-990
This data paper reports litter fall data collected in a network of 21 forest sites in Japan. This is the largest litter fall data set freely available in Japan to date. The network is a part of the Monitoring Sites 1000 Project launched by the Ministry of the Environment, Japan. It covers subarctic to subtropical climate zones and the four major forest types in Japan. Twenty-three permanent plots in which usually 25 litter traps were installed were established in old-growth or secondary natural forests. Litter falls were collected monthly from 2004, and sorted into leaves, branches, reproductive structures and miscellaneous. The data provide seasonal patterns and inter-annual dynamics of litter falls, and their geographical patterns, and offer good opportunities for meta-analyses and comparative studies among forests. 相似文献
80.
Nishimura J Saiga H Sato S Okuyama M Kayama H Kuwata H Matsumoto S Nishida T Sawa Y Akira S Yoshikai Y Yamamoto M Takeda K 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(6):4032-4039
Secretory leukocyte protease inhibitor (SLPI) has multiple functions, including inhibition of protease activity, microbial growth, and inflammatory responses. In this study, we demonstrate that mouse SLPI is critically involved in innate host defense against pulmonary mycobacterial infection. During the early phase of respiratory infection with Mycobacterium bovis bacillus Calmette-Guérin, SLPI was produced by bronchial and alveolar epithelial cells, as well as alveolar macrophages, and secreted into the alveolar space. Recombinant mouse SLPI effectively inhibited in vitro growth of bacillus Calmette-Guérin and Mycobacterium tuberculosis through disruption of the mycobacterial cell wall structure. Each of the two whey acidic protein domains in SLPI was sufficient for inhibiting mycobacterial growth. Cationic residues within the whey acidic protein domains of SLPI were essential for disruption of mycobacterial cell walls. Mice lacking SLPI were highly susceptible to pulmonary infection with M. tuberculosis. Thus, mouse SLPI is an essential component of innate host defense against mycobacteria at the respiratory mucosal surface. 相似文献