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151.
Bahrudin U Morikawa K Takeuchi A Kurata Y Miake J Mizuta E Adachi K Higaki K Yamamoto Y Shirayoshi Y Yoshida A Kato M Yamamoto K Nanba E Morisaki H Morisaki T Matsuoka S Ninomiya H Hisatome I 《Journal of molecular biology》2011,413(4):857-878
Cardiac arrhythmogenesis is regulated by channel proteins whose protein levels are in turn regulated by the ubiquitin-proteasome system (UPS). We have previously reported on UPS impairment induced by E334K cardiac myosin-binding protein C (cMyBPC), which causes hypertrophic cardiomyopathy (HCM) accompanied by arrhythmia. We hypothesized that UPS impairment induced by E334K cMyBPC causes accumulation of cardiac channel proteins, leading to electrophysiological dysfunction. Wild-type or E334K cMyBPC was overexpressed in HL-1 cells and primary cultured neonatal rat cardiac myocytes. The expression of E334K cMyBPC suppressed cellular proteasome activities. The protein levels of Kv1.5, Nav1.5, Hcn4, Cav3.2, Cav1.2, Serca, RyR2, and Ncx1 were significantly higher in cells expressing E334K cMyBPC than in wild type. They further increased in cells pretreated with MG132 and had longer protein decays. The channel proteins retained the correct localization. Cells expressing E334K cMyBPC exhibited higher Ca2+ transients and longer action potential durations (APDs), accompanied by afterdepolarizations and higher apoptosis. Those augments of APD and Ca2+ transients were recapitulated by a simulation model. Although a Ca2+ antagonist, azelnidipine, neither protected E334K cMyBPC from degradation nor affected E334K cMyBPC incorporation into the sarcomere, it normalized the APD and Ca2+ transients and partially reversed the levels of those proteins regulating apoptosis, thereby attenuating apoptosis. In conclusion, UPS impairment caused by E334K cMyBPC may modify the levels of channel proteins, leading to electrophysiological dysfunction. Therefore, UPS impairment due to a mutant cMyBPC may partly contribute to the observed clinical arrhythmias in HCM patients. 相似文献
152.
Shimoda H Ninomiya K Nishida N Yoshino T Morikawa T Matsuda H Yoshikawa M 《Bioorganic & medicinal chemistry letters》2003,13(2):223-228
The methanolic extract from the leaves of artichoke (Cynara scolymus L.) was found to suppress serum triglyceride elevation in olive oil-loaded mice. Through bioassay-guided separation, sesquiterpenes (cynaropicrin, aguerin B, and grosheimin) were isolated as the active components together with new sesquiterpene glycosides (cynarascolosides A, B, and C). The oxygen functional groups at the 3- and 8-positions and exo-methylene moiety in alpha-methylene-gamma-butyrolactone ring were found to be essential for the anti-hyperlipidemic activity of guaiane-type sesquiterpene. In addition, inhibition of gastric emptying was shown to be partly involved in anti-hyperlipidemic activity. 相似文献
153.
Masaki Fukuda Yu Komatsu Hironao Yamada Ryota Morikawa Takeshi Miyakawa Masako Takasu 《Molecular simulation》2014,40(6):498-503
Rational design of protein surface is important for creating higher order protein structures, but it is still challenging. In this study, we designed in silico the several binding interfaces on protein surfaces that allow a de novo protein–protein interaction to be formed. We used a computer simulation technique to find appropriate amino acid arrangements for the binding interface. The protein–protein interaction can be made by forming an intermolecular four-helix bundle structure, which is often found in naturally occurring protein subunit interfaces. As a model protein, we used a helical protein, YciF. Molecular dynamics simulation showed that a new protein–protein interaction is formed depending on the number of hydrophobic and charged amino acid residues present in the binding surfaces. However, too many hydrophobic amino acid residues present in the interface negatively affected on the binding. Finally, we found an appropriate arrangement of hydrophobic and charged amino acid residues that induces a protein–protein interaction through an intermolecular four-helix bundle formation. 相似文献
154.
Yohey Suzuki Uta Konno Akari Fukuda Daisuke D. Komatsu Akinari Hirota Katsuaki Watanabe Yoko Togo Noritoshi Morikawa Hiroki Hagiwara Daisuke Aosai Teruki Iwatsuki Urumu Tsunogai Seiya Nagao Kazumasa Ito Takashi Mizuno 《PloS one》2014,9(12)
In contrast to the deep subseafloor biosphere, a volumetrically vast and stable habitat for microbial life in the terrestrial crust remains poorly explored. For the long-term sustainability of a crustal biome, high-energy fluxes derived from hydrothermal circulation and water radiolysis in uranium-enriched rocks are seemingly essential. However, the crustal habitability depending on a low supply of energy is unknown. We present multi-isotopic evidence of microbially mediated sulfate reduction in a granitic aquifer, a representative of the terrestrial crust habitat. Deep meteoric groundwater was collected from underground boreholes drilled into Cretaceous Toki granite (central Japan). A large sulfur isotopic fractionation of 20–60‰ diagnostic to microbial sulfate reduction is associated with the investigated groundwater containing sulfate below 0.2 mM. In contrast, a small carbon isotopic fractionation (<30‰) is not indicative of methanogenesis. Except for 2011, the concentrations of H2 ranged mostly from 1 to 5 nM, which is also consistent with an aquifer where a terminal electron accepting process is dominantly controlled by ongoing sulfate reduction. High isotopic ratios of mantle-derived 3He relative to radiogenic 4He in groundwater and the flux of H2 along adjacent faults suggest that, in addition to low concentrations of organic matter (<70 µM), H2 from deeper sources might partly fuel metabolic activities. Our results demonstrate that the deep biosphere in the terrestrial crust is metabolically active and playing a crucial role in the formation of reducing groundwater even under low-energy fluxes. 相似文献
155.
In order to understand a role of the Ca(2+) ion on the structure and function of a Ca(2+)-dependent family I.3 lipase from Pseudomonas sp. MIS38, apo-PML, holo-PML, holo-PML*, and the N-terminal domain alone (N-fragment) were prepared and biochemically characterized. Apo-PML and holo-PML represent refolded proteins in the absence and presence of the Ca(2+) ion, respectively. Holo-PML* represents a holo-PML dialyzed against 20 mM Tris-HCl (pH 7.5). The results suggest that the C-terminal domain of PML is almost fully unfolded in the apo-form and its folding is induced by Ca(2+) binding. The folding of this C-terminal domain may be required to make a conformation of the N-terminal catalytic domain functional. 相似文献
156.
Mikio Kawamori Yasushi Morikawa Seigo Takasawa 《Applied microbiology and biotechnology》1985,22(3):235-236
Summary L-Sorbose, which is known as an inhibitor of -1,3-glucan synthesis in fungi, induces the production of cellulases in strains belonging to Trichoderma reesei. Especially, mutant strains PC-3–7 and X-31, which were obtained by several steps of mutation from QM 9414, have the most effective cellulase inducibility by L-sorbose comparing with other mutants of Trichoderma reesei. They synthesized cellulases effectively in liquid culture, whenever the alkaline treated sugarcane bagasse was used as a main carbon source for lowering the cost of cellulase production. 相似文献
157.
The administration--timing-dependent therapeutic effects of bleomycin (BLM) were observed on a fibrosarcoma implanted SC in WKA rats. Five consecutive IP administrations of BLM (5 mg/kg/d) were found to be more effective when BLM was given from Day 8 than when it was given from Day 1 for tumors implanted on Day 0. The therapeutic effects correlated well with antitumor immune responses, which were examined on Day 13 when the tumor had not yet regressed even in surviving rats. The tumor-neutralizing activity of spleen cells was augmented in rats treated with BLM from Day 8 to Day 12, and the suppressor cell activity detected in the spleen cells of tumor-bearing rats was eliminated by the BLM treatment. The tumoricidal activity of peritoneal exudate cells (PEC) was detected in rats treated from Day 8 but not in rats untreated or treated from Day 1. The in vitro treatment of KMT-17 cells with BLM (20 micrograms/ml) for two hours enhanced the sensitivity of the tumor cells to the activity of tumoricidal PEC. This suggests that the direct action of BLM on tumor cells also plays an immunologic role in BLM treatment. The findings reveal that the therapeutic effect of BLM is elicited by its ability to augment the host immune responses to tumor cells. 相似文献
158.
M Takeyama K Kondo A Otaka S Asakura N Morikawa S Itami S Takayasu N Fujii 《Biochemical and biophysical research communications》1991,180(1):455-461
The concentration of gastrin releasing peptide-like immunoreactive substance (GRP-IS) was measured by enzyme immunoassay (EIA) in rat mammary glands during pregnancy and after delivery. The GRP-IS concentration was high in the middle stage of pregnancy (10-14 days of gestation) and decreased in late pregnancy to reach a plateau range. By using HPLC, it was shown that GRP(20-29) and GRP(16-29) were mainly present in rat mammary glands. Immunohistochemical study revealed that epithelial cells of rat mammary glands were stained intensely with antiserum GP-6201. These results suggest that GRP-IS is produced and secreted in epithelial cells of mammary glands and takes part in the proliferation, differentiation and hypertrophy of mammary glands. 相似文献
159.
Involvement of ralfuranones in the quorum sensing signalling pathway and virulence of Ralstonia solanacearum strain OE1‐1
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160.
Characterization of three strains of Capnocytophaga canis isolated from patients with sepsis
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Michio Suzuki Koichi Imaoka Yumi Haga Masahiro Mohri Ayako Nogami Yoshio Shimojima Yoshimi Irie Satoru Sugimura Shigeru Morikawa 《Microbiology and immunology》2018,62(9):567-573