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811.
Yoshitomo Morinaga Katsunori Yanagihara Shigeki Nakamura Hiroo Hasegawa Masafumi Seki Koichi Izumikawa Hiroshi Kakeya Yoshihiro Yamamoto Yasuaki Yamada Shigeru Kohno Shimeru Kamihira 《Respiratory research》2010,11(1):158
Background
Legionella pneumophila (LPN) can cause a lethal infectious disease with a marked inflammatory response in humans. However, the mechanism of this severe inflammation remains poorly understood. Since necrosis is known to induce inflammation, we investigated whether LPN induces necrosis in macrophages. We also analyzed the involvement of lysosomal cathepsin B in LPN-induced cell death.Methods
The human monocytic cell line THP-1 was infected with LPN, NUL1 strain. MG132-treated cells were used as apoptotic control cells. After infection, the type of cell death was analyzed by using microscopy, LDH release and flow cytometry. As a proinflammatory mediator, high-mobility group box 1 (HMGB-1), was measured. Cathepsin B activity was also measured and the inhibitory effects of cathepsin B on LPN-induced cell death were analyzed.Results
THP-1 cells after treatment with high dose of LPN showed necrotic features with releasing HMGB-1. This necrosis and the HMGB-1 release were inhibited by a specific lysosomal cathepsin B inhibitor and were characterized by a rapid and high activation of cathepsin B that was not observed in apoptotic control cells. The necrosis was also accompanied by cathepsin B-dependent poly(ADP-ribose) polymerase (PARP) cleavage.Conclusions
We demonstrate here that L. pneumophila rapidly induces cathepsin B-dependent necrosis in a dose-dependent manner and releases a proinflammatory mediator, HMGB-1, from macrophages. This report describes a novel aspect of the pathogenesis of Legionnaires'' disease and provides a possible therapeutic target for the regulation of inflammation. 相似文献812.
Nagib Ahsan Yohei Nanjo Hiroko Sawada Yoshihisa Kohno Setsuko Komatsu 《Proteomics》2010,10(14):2605-2619
Considerable soybean yield losses caused by ozone (O3) stress have been demonstrated by large‐scale meta‐analyses of free‐gas concentration enrichment systems. In this study, comparative proteomic approach was employed to explore the differential changes of proteins in O3 target structures such as leaf and chloroplasts of soybean seedlings. Acute O3 exposure (120 parts‐per‐billion) for 3 days did not cause any visible symptoms in developing leaves. However, higher amounts of ROS and lipid peroxidation indicated that severe oxidative burst occurred. Immunoblot analysis of O3‐induced known proteins revealed that proteins were modulated before symptoms became visible. Proteomic analysis identified a total of 20 and 32 differentially expressed proteins from O3‐treated leaf and chloroplast, respectively. Proteins associated with photosynthesis, including photosystem I/II and carbon assimilation decreased following exposure to O3. In contrast, proteins involved in antioxidant defense and carbon metabolism increased. The activity of enzymes involved in carbohydrate metabolism increased following exposure to O3, which is consistent with the decrease in starch and increase in sucrose concentrations. Taken together, these results suggest that carbon allocation is tightly programmed, and starch degradation probably feeds the tricarboxylic acid cycle while the photosynthesis pathway is severely affected during O3 stress. 相似文献
813.
Guo-Qiang Bi Vadim Bolshakov Guojun Bu Catherine M Cahill Zhou-Feng Chen Graham L Collingridge Robin L Cooper Jens R Coorssen Alaa El-Husseini Vasco Galhardo Wen-Biao Gan Jianguo Gu Kazuhide Inoue John Isaac Koichi Iwata Zhengping Jia Bong-Kiun Kaang Mikito Kawamata Satoshi Kida Eric Klann Tatsuro Kohno Min Li Xiao-Jiang Li John F MacDonald Karim Nader Peter V Nguyen Uhtaek Oh Ke Ren John C Roder Michael W Salter Weihong Song Shuzo Sugita Shao-Jun Tang Yuanxiang Tao Yu Tian Wang Newton Woo Melanie A Woodin Zhen Yan Megumu Yoshimura Ming Xu Zao C Xu Xia Zhang Mei Zhen Min Zhuo 《Molecular pain》2006,2(1):1-22
Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21–23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29–31, 2007). 相似文献
814.
Kobayashi Y Kohno N Wanibe S Hirayasu K Uemori H Tagawa Y Yokoyama T Shinagawa M 《Analytical biochemistry》2006,349(2):218-228
The precise diagnosis for bovine spongiform encephalopathy (BSE) is crucial for preventing new transmission to humans. Several testing procedures are reported for determining protease-resistant prion protein in various tissues as a major hallmark of prion diseases such as BSE, scrapie, and Creutzfeldt-Jakob disease. However, contamination of materials from tissues or degradation of the specimens sometimes disturbs the accuracy of the assay. Here, we have developed a novel method for solid-phase immunoassay of the disease-specific conformational isoform, PrP(Sc), using filtration blotting of protein in the presence of sodium dodecyl sulfate (SDS) followed by a filtration-based immunoassay with a single anti-prion protein antibody, together with the improved fractionation procedure involving high concentrations of surfactant/detergent. The SDS/heat treatment renders unfolded PrP(Sc) quantitative retention on a polyvinylidene difluoride filter and allows enhancement of the analyte signal with immunodetection; thus, all of the tested specimens are determined with 100% accuracy. In addition, the immunoassay is completed in approximately 1h, indicating its usefulness not only for the screening of BSE specimens but probably also for the postmortem BSE diagnosis of fallen stock as the antibody recognizes the core part of PrP(Sc). The solid-phase immunoassay method, including the filtration blotting with SDS, would be applicable to determining even more sensitively proteins other than PrP(Sc), especially those having rigid conformations. 相似文献
815.
816.
Structure of tightly membrane-bound mastoparan-X, a G-protein-activating peptide, determined by solid-state NMR 下载免费PDF全文
Todokoro Y Yumen I Fukushima K Kang SW Park JS Kohno T Wakamatsu K Akutsu H Fujiwara T 《Biophysical journal》2006,91(4):1368-1379
The structure of mastoparan-X (MP-X), a G-protein activating peptide from wasp venom, in the state tightly bound to anionic phospholipid bilayers was determined by solid-state NMR spectroscopy. Carbon-13 and nitrogen-15 NMR signals of uniformly labeled MP-X were completely assigned by multidimensional intraresidue C-C, N-CalphaCbeta, and N-Calpha-C', and interresidue Calpha-CalphaCbeta, N-CalphaCbeta, and N-C'-Calpha correlation experiments. The backbone torsion angles were predicted from the chemical shifts of 13C', 13Calpha, 13Cbeta, and 15N signals with the aid of protein NMR database programs. In addition, two 13C-13C and three 13C-15N distances between backbone nuclei were precisely measured by rotational resonance and REDOR experiments, respectively. The backbone structure of MP-X was determined from the 26 dihedral angle restraints and five distances with an average root-mean-square deviation of 0.6 A. Peptide MP-X in the bilayer-bound state formed an amphiphilic alpha-helix for residues Trp3-Leu14 and adopted an extended conformation for Asn2. This membrane-bound conformation is discussed in relation to the peptide's activities to form pores in membranes and to activate G-proteins. This study demonstrates the power of multidimensional solid-state NMR of uniformly isotope-labeled molecules and distance measurements for determining the structures of peptides bound to lipid membranes. 相似文献
817.
818.
Fujiwara Y Kawada K Takano D Tanimura S Ozaki K Kohno M 《Biochemical and biophysical research communications》2006,340(2):560-566
Constitutive activation of the PI3 kinase/Akt pathway is associated with the neoplastic phenotype of a large number of human tumor cells. As the anti-apoptotic role of the PI3 kinase/Akt pathway has been established, we have examined whether specific blockade of this pathway sensitizes tumor cells to DNA-damaging agent-induced cytotoxicity by enhancing apoptotic cell death. Although a PI3 kinase inhibitor, LY294002, by itself does not induce apoptotic cell death, LY294002 selectively and markedly enhances the apoptosis-inducing efficacy of doxorubicin: such an enhanced cell death is only detected in tumor cells in which the PI3 kinase/Akt pathway is constitutively activated, and it is totally dependent on the functional p53 pathway. These results suggest that the combination of a PI3 kinase/Akt pathway inhibitor and doxorubicin provides an efficient chemotherapeutic strategy for the treatment of tumor cells in which the PI3 kinase/Akt pathway is constitutively activated and the p53 pathway is functional. 相似文献
819.
Ozaki K Minoda A Kishikawa F Kohno M 《Biochemical and biophysical research communications》2006,339(4):1171-1177
Constitutive activation of the extracellular signal-regulated kinase (ERK) pathway is associated with the neoplastic phenotype of a large number of human tumor cells. Although specific blockade of the ERK pathway by treating such tumor cells with potent mitogen-activated protein kinase/ERK kinase (MEK) inhibitors completely suppresses their proliferation, it by itself shows only a modest effect on the induction of apoptotic cell death. However, these MEK inhibitors markedly enhance the efficacy of histone deacetylase (HDAC) inhibitors to induce apoptotic cell death: such an enhanced cell death is observed only in tumor cells in which the ERK pathway is constitutively activated. Co-administration of MEK inhibitor markedly sensitizes tumor cells to HDAC inhibitor-induced generation of reactive oxygen species, which appears to mediate the enhanced cell death induced by the combination of these agents. These results suggest that the combination of MEK inhibitors and HDAC inhibitors provides an efficient chemotherapeutic strategy for the treatment of tumor cells in which the ERK pathway is constitutively activated. 相似文献
820.
Chromosome interstitial deletion (i.e., deletion of a chromosome segment in a chromosome arm) is a critical genetic event for the inactivation of tumor suppressor genes and activation of oncogenes leading to the carcinogenic conversion of human cells. The deletion at chromosome 9p21 removing the p16 tumor suppressor gene is a genetic alteration frequently observed in a variety of human cancers. Thus, structural analyses of breakpoints for p16 deletions in several kinds of human cancers have been performed to elucidate the molecular process of chromosome interstitial deletion consisting of formation of DNA double strand breaks (DSBs) and subsequent joining of DNA ends in human cells. The results indicated that DSBs triggering deletions in lymphoid leukemia are formed at a few defined sites by illegitimate action of the RAG protein complex, while DSBs in solid tumors are formed at unspecific sites by factors unidentified yet. In both types of tumors, the intra-nuclear architecture of chromatin was considered to affect the susceptibility of genomic segments of the p16 locus to DSBs. Broken DNA ends were joined by non-homologous end joining (NHEJ) repair in both types of tumors, however, microhomologies of DNA ends were preferentially utilized in the joining in solid tumors but not in lymphoid leukemia. The configuration of broken DNA ends as well as NHEJ activity in cells was thought to underlie the features of joining. Further structural analysis of other hot spots of chromosomal DNA breaks as well as the evaluation of the activity and specificity of NHEJ in human cells will elucidate the mechanisms of chromosome interstitial deletions in human cells. 相似文献