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911.
Mohammad Omar Faruk Yoshinobu Ichimura Shun Kageyama Satoko Komatsu-Hirota Afnan H. El-Gowily Yu-shin Sou Masato Koike Nobuo N. Noda Masaaki Komatsu 《The Journal of biological chemistry》2021,297(6)
Several amyotrophic lateral sclerosis (ALS)-related proteins such as FUS, TDP-43, and hnRNPA1 demonstrate liquid–liquid phase separation, and their disease-related mutations correlate with a transition of their liquid droplet form into aggregates. Missense mutations in SQSTM1/p62, which have been identified throughout the gene, are associated with ALS, frontotemporal degeneration (FTD), and Paget’s disease of bone. SQSTM1/p62 protein forms liquid droplets through interaction with ubiquitinated proteins, and these droplets serve as a platform for autophagosome formation and the antioxidative stress response via the LC3-interacting region (LIR) and KEAP1-interacting region (KIR) of p62, respectively. However, it remains unclear whether ALS/FTD-related p62 mutations in the LIR and KIR disrupt liquid droplet formation leading to defects in autophagy, the stress response, or both. To evaluate the effects of ALS/FTD-related p62 mutations in the LIR and KIR on a major oxidative stress system, the Keap1-Nrf2 pathway, as well as on autophagic turnover, we developed systems to monitor each of these with high sensitivity. These methods such as intracellular protein–protein interaction assay, doxycycline-inducible gene expression system, and gene expression into primary cultured cells with recombinant adenovirus revealed that some mutants, but not all, caused reduced NRF2 activation and delayed autophagic cargo turnover. In contrast, while all p62 mutants demonstrated sufficient ability to form liquid droplets, all of these droplets also exhibited reduced inner fluidity. These results indicate that like other ALS-related mutant proteins, p62 missense mutations result in a primary defect in ALS/FTD via a qualitative change in p62 liquid droplet fluidity. 相似文献
912.
Kazumasa Fujitani Jun-ichi Kambayashi Hideo Ariyoshi Masato Sakon Shinobu Imajoh-Ohmi Takashi Nakamura Morito Monden 《Journal of cellular biochemistry》1997,66(1):54-64
Fluid shear stress has been known to activate platelet reaction such as aggregation, but the exact mechanism of shear-induced platelet aggregation (SIPA) has not been fully understood. Calpain, an intracellular calcium-activated cysteine protease, is abundant in platelets and is considered to be activated and involved in the proteolytic processes during platelet activation. A possible activation of calpain in SIPA was investigated, employing a newly developed aggregometer and specific monoclonal antibodies to detect activation of calpain. When a shear stress gradient varying between 6 and 108 dyn/cm2 was applied to platelets, activation of μ-calpain was observed only in high-shear-stressed platelets, resulting in the proteolysis of talin. At 1 min after the onset of constant high shear stress of 108 dyn/cm2, μ-calpain activation and proteolysis of talin were detected and increased in a time-dependent manner. Constant shear stress more than 50 dyn/cm2, applied for 5 min, caused μ-calpain activation and proteolysis of talin, which were increased in a shear-force-dependent manner. Calpeptin, a calpain-specific peptide antagonist, caused the complete inhibition of both μ-calpain activation and proteolysis of talin, while SIPA profiles with calpeptin showed almost no change compared to those without calpeptin. These results suggest the possibility of calpain involvement in late phases of shear-induced platelet activation such as cytoskeletal reorganization. J. Cell. Biochem. 66:54–64, 1997. © 1997 Wiley-Liss, Inc. 相似文献
913.
914.
Quasispecies of TT Virus (TTV) with Sequence Divergence in Hypervariable Regions of the Capsid Protein in Chronic TTV Infection 总被引:17,自引:0,他引:17 下载免费PDF全文
Tsutomu Nishizawa Hiroaki Okamoto Fumio Tsuda Tatsuya Aikawa Yoshiki Sugai Keiko Konishi Yoshihiro Akahane Masato Ukita Takeshi Tanaka Yuzo Miyakawa Makoto Mayumi 《Journal of virology》1999,73(11):9604-9608
Three hypervariable regions were identified in a central portion of open reading frame 1 of TT virus DNA, which codes for a putative capsid protein of 770 amino acids. TT virus circulates as quasispecies, with many amino acid substitutions in hypervariable regions, to evade immune surveillance of the hosts and to establish a persistent infection. 相似文献
915.
Avirulent Avian Influenza Virus as a Vaccine Strain against a Potential Human Pandemic 总被引:8,自引:0,他引:8 下载免费PDF全文
Ayato Takada Noritaka Kuboki Katsunori Okazaki Ai Ninomiya Hiroko Tanaka Hiroichi Ozaki Shigeyuki Itamura Hidekazu Nishimura Masayoshi Enami Masato Tashiro Kennedy F. Shortridge Hiroshi Kida 《Journal of virology》1999,73(10):8303-8307
In the influenza H5N1 virus incident in Hong Kong in 1997, viruses that are closely related to H5N1 viruses initially isolated in a severe outbreak of avian influenza in chickens were isolated from humans, signaling the possibility of an incipient pandemic. However, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system because of the lethality of the virus for chicken embryos and the high level of biosafety therefore required for vaccine production. Alternative approaches, including an avirulent H5N4 virus isolated from a migratory duck as a surrogate virus, H5N1 virus as a reassortant with avian virus H3N1 and an avirulent recombinant H5N1 virus generated by reverse genetics, have been explored. All vaccines were formalin inactivated. Intraperitoneal immunization of mice with each of vaccines elicited the production of hemagglutination-inhibiting and virus-neutralizing antibodies, while intranasal vaccination without adjuvant induced both mucosal and systemic antibody responses that protected the mice from lethal H5N1 virus challenge. Surveillance of birds and animals, particularly aquatic birds, for viruses to provide vaccine strains, especially surrogate viruses, for a future pandemic is stressed. 相似文献
916.
Hirohiko Ise Seiji Takashima Masato Nagaoka Anwarul Ferdous Toshihiro Akaike 《Biotechnology letters》1999,21(3):209-213
Three-dimensional (3D) and two-dimensional (2D) cultures of hepatocytes in various concentrations (0.3–0.7%) of agarose gel revealed that the hepatocytes under 3D cultures in 0.3% agarose gel possess long-term (>3 weeks) viability, significant self-assembly to form tissue like aggregates, low lactate dehydrogenase release and high albumin synthesis. These were in contrast to 2D culture of hepatocytes. Our results suggest that the 3D culture of hepatocytes in agarose gel favors aggregate formation of functionally active cells and would be useful for liver transplantation as well as to analyze hepatocytes biology. 相似文献
917.
918.
Masataka Ikeda Hideo Ariyoshi Jun-ichi Kambayashi Kazumasa Fujitani Nobutoshi Shinoki Masato Sakon Tomio Kawasaki Morito Monden 《Journal of cellular biochemistry》1996,63(1):23-36
Ca2+ concentration inside human umbilical vein endothelial cells was studied separately in cytosol and nucleus by a confocal laser scanning microscopy using fluo-3. The in vivo calibration curve for cytosol and nucleus showed good linearity between fluorescence intensity and Ca2+ concentration in cytosol ([Ca2+]i) and nuclei ([Ca2+]n). After calibration, [Ca2+]n was constantly higher than [Ca2+]i before and after the chelation of extracellular Ca2+ suggesting an active Ca2+ accumulation system on nuclear membrane. [Ca2+]n was also constantly higher than [Ca2+]i after the stimulation of thrombin (0.05 U/ml), FCS (10%), and thapsigargin (Tsg, 1μM). The temporal change of [Ca2+]n and [Ca2+]i was identical, and [Ca2+]i gradient towards the nucleus and peripheral or central [Ca2+]n rise was observed after these stimulations. From these results, [Ca2+]n is not only regulated by the active Ca2+ accumulation system on nuclear membrane at rest but also the generation of Inositol-triphosphate. FCS caused heterogeneous [Ca2+]n or [Ca2+]i rise from cell to cell; single spike or oscillatory change of [Ca2+]n and [Ca2+]i was observed in about 56% of cells, which were completely abolished by the chelation of extracellular Ca2+, suggesting that FCS stimulated [Ca2+]n and [Ca2+]i rise solely depending on Ca2+ influx from extracellular medium. The higher concentration of [Ca2+]n and heterogeneous [Ca2+]n rise may have important roles in nuclear-specific cellular responses. © 1996 Wiley-Liss, Inc. 相似文献
919.
Masato Watanabe Kanji Uchida Kazuhide Nakagaki Bruce C. Trapnell Koh Nakata 《Cytokine & growth factor reviews》2010,21(4):263-273
Numerous reports have documented the presence of autoantibodies working against naturally occurring cytokines in humans in health and disease. In most instances, their physiological and pathophysiological significance remains unknown. However, recent advances in the methodologies for detecting cytokine autoantibodies and their application in research focused on specific disorders have shown that some cytokine autoantibodies play an important role in the pathogenesis of disease. Additionally, levels of cytokine autoantibodies may also correlate with disease severity and progression in certain infectious and autoimmune diseases but not in others. This suggests that cytokine-specific pathogenic differences exist. While multiple lines of evidence support the notion that high avidity cytokine autoantibodies are present and likely to be ubiquitous in healthy individuals, their potential physiological role, if any, is less clear. It is believed that they may function by scavenging pro-inflammatory cytokines and thereby inhibiting deleterious ‘endocrine’ effects, or by serving as carrier proteins, providing a ‘reservoir’ of inactive cytokines and thus modulating cytokine bioactivity. A central hypothesis is that sustained or repeated high-level exposure to cytokines triggers defects in T-cell tolerance, resulting in the expansion of existing cytokine autoantibody-producing B cells. 相似文献
920.
Kei'ichi Baba ;Yong Woo Park ;Tomomi Kaku ;Rumi Kaida ;Miyuki Takeuchi ;Masato Yoshida ;Yoshihiro Hosoo ;Yasuhisa Ojio ;Takashi Okuyama ;Toru Taniguchi ;Yasunori Ohmiya ;Teiji Kondo ;Ziv Shani ;Oded Shoseyov ;Tatsuya Awano ;Satoshi Serada ;Naoko Norioka ;Shigemi Norioka ;Takahisa Hayashi 《植物生理学报》2009,(5):893-903
In response to environmental variation, angiosperm trees bend their stems by forming tension wood, which consists of a cellulose-rich G (gelatinous)-Iayer in the walls of fiber cells and generates abnormal tensile stress in the secondary xylem. We produced transgenic poplar plants overexpressing several endoglycanases to reduce each specific polysaccharide in the cell wall, as the secondary xylem consists of primary and secondary wall layers. When placed horizontally, the basal regions of stems of transgenic poplars overexpressing xyloglucanase alone could not bend upward due to low strain in the tension side of the xylem. In the wild-type plants, xyloglucan was found in the inner surface of G-layers during multiple layering. In situ xyloglucan endotransglucosylase (XET) activity showed that the incorporation of whole xyloglucan, potentially for wall tightening, began at the inner surface layers S1 and S2 and was retained throughout G-layer development, while the incorporation of xyloglucan heptasaccharide (XXXG) for wall loosening occurred in the primary wall of the expanding zone. We propose that the xyloglucan network is reinforced by XET to form a further connection between wall-bound and secreted xyloglucans in order to withstand the tensile stress created within the cellulose G-layer micro fibrils. 相似文献