17 results on '"Sasagawa N"'
Search Results
2. Clinical Nephrology - Lab methods and other markers
- Author
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Kleophas, W., primary, Bieber, B., additional, Robinson, B., additional, Duttlinger, J., additional, Fliser, D., additional, Lonneman, G., additional, Rump, L., additional, Pisoni, R., additional, Port, F., additional, Reichel, H., additional, Daniela, R., additional, Ciocalteu, A., additional, Checherita, I. A., additional, Peride, I., additional, Spataru, D. M., additional, Niculae, A., additional, Laetitia, K., additional, Amna, K., additional, Laurence, D., additional, Aoumeur, H.-A., additional, Flamant, M., additional, Haymann, J.-P., additional, Letavernier, E., additional, Vidal-Petiot, E., additional, Boffa, J.-J., additional, Vrtovsnik, F., additional, Bianco, F., additional, Pessolano, G., additional, Carraro, M., additional, Panzetta, G. O., additional, Ebert, N., additional, Gaedeke, J., additional, Jakob, O., additional, Kuhlmann, M., additional, Martus, P., additional, Van der Giet, M., additional, Scha ner, E., additional, Khan, I., additional, Law, Y., additional, Turgutalp, K., additional, Ozhan, O., additional, Gok Oguz, E., additional, Kiykim, A., additional, Donadio, C., additional, Hatmi, Z. N., additional, Mahdavi-Mazdeh, M., additional, Morales, E., additional, Gutierrez-Millet, V., additional, Rojas-Rivera, J., additional, Huerta, A., additional, Gutierrez, E., additional, Gutierrez-Solis, E., additional, Polanco, N., additional, Caro, J., additional, Gonza z, E., additional, Praga, M., additional, Marco Mayayo, M., additional, Valdivielso, J., additional, Marti z, M., additional, Fernaez Giraez, E., additional, Obrador, G., additional, Olvera, N., additional, Ortiz de la Pe, D., additional, Gutie ez, V., additional, Villa, A., additional, Redal-Baigorri, B., additional, Sombolos, K., additional, Tsakiris, D., additional, Boletis, J., additional, Vlahakos, D., additional, Siamopoulos, K., additional, Vargiemezis, V., additional, Nikolaidis, P., additional, Iatrou, C., additional, Dafnis, E., additional, Argyropoulos, C., additional, Xynos, K., additional, Schock-Kusch, D., additional, Shulhevich, Y., additional, Geraci, S., additional, Hesser, J., additional, Stsepankou, D., additional, Neudecker, S., additional, Koenig, S., additional, Hoecklin, F., additional, Pill, J., additional, Gretz, N., additional, Schweda, F., additional, Schreiber, A., additional, Kudo, K., additional, Konta, T., additional, Choi, S. O., additional, Kim, J. S., additional, Kim, M. K., additional, Yang, J. W., additional, Han, B. G., additional, Delanaye, P., additional, Cavalier, E., additional, Masson, I., additional, Mehdi, M., additional, Nicolas, M., additional, Lambermont, B., additional, Dubois, B., additional, Damas, P., additional, Krzesinski, J.-M., additional, Morel, J., additional, Lautrette, A., additional, Christophe, M., additional, Gagneux-Brunon, A., additional, Anne, F., additional, Fre (C)ric, L., additional, Bevc, S., additional, Ekart, R., additional, Hojs, R., additional, Gorenjak, M., additional, Puklavec, L., additional, Hashimoto, N., additional, Suzuki, A., additional, Mitsumoto, K., additional, Shimizu, M., additional, Niihata, K., additional, Kawabata, A., additional, Sakaguchi, Y., additional, Hayashi, T., additional, Shoji, T., additional, Okada, N., additional, Tsubakihara, Y., additional, Hamano, T., additional, Nakano, C., additional, Fujii, N., additional, Obi, Y., additional, Mikami, S., additional, Inoue, K., additional, Matsui, I., additional, Isaka, Y., additional, Rakugi, H., additional, Edvardsson, V., additional, Siguron, B., additional, Thorsteinsdottir, M., additional, Palsson, R., additional, Matsumoto, J., additional, Miyazaki, N., additional, Murata, I., additional, Yoshida, G., additional, Morishita, K., additional, Ushikoshi, H., additional, Nishigaki, K., additional, Ogura, S., additional, Minatoguchi, S., additional, Werneke, U., additional, Ott, M., additional, Salander-Renberg, E., additional, Taylor, D., additional, Stegmayr, B., additional, Surel, S., additional, Wenzlova, M., additional, Silva Junior, G., additional, Vieira, A. P., additional, Couto Bem, A., additional, Alves, M., additional, Torres, A., additional, Meneses, G., additional, Martins, A., additional, Liborio, A., additional, Daher, E., additional, Gluhovschi, G., additional, Modilca, M., additional, Daminescu, L., additional, Gluhovschi, C., additional, Velciov, S., additional, Petrica, L., additional, Gadalean, F., additional, Balgradean, C., additional, Schmeiser, H. H., additional, Kolesnyk, M., additional, Stepanova, N., additional, Surzhko, L., additional, Stashevska, N., additional, Filiopoulos, V., additional, Hadjiyannakos, D., additional, Arvanitis, D., additional, Panagiotopoulos, K., additional, Vlassopoulos, D., additional, Kaesler, N., additional, Schettgen, T., additional, Magdeleyns, E., additional, Brandenburg, V., additional, Vermeer, C., additional, Floege, J., additional, Kr, T., additional, Randone, O., additional, Ferraresi, M., additional, Aroasio, E., additional, Depascale, A., additional, Scognamiglio, S., additional, Consiglio, V., additional, Piccoli, G. B., additional, Jensen, L. V., additional, Lizakowski, S., additional, Rutkowski, P., additional, Tylicki, L., additional, Renke, M., additional, Sulikowska, B., additional, Donderski, R., additional, Bednarski, R., additional, Heleniak, Z., additional, Przybylska, M., additional, Manitius, J., additional, Rutkowski, B., additional, Bobrova, L., additional, Kozlovskaya, N., additional, Kanayama, K., additional, Hasegawa, M., additional, Kitagawa, F., additional, Ishii, J., additional, Yuzawa, Y., additional, Tanaka, K., additional, Sakai, K., additional, Hara, S., additional, Suzuki, Y., additional, Tanaka, Y., additional, Aikawa, A., additional, Hinoshita, F., additional, Hamano, N., additional, Sasaki, E., additional, Kato, A., additional, Katsuki, T., additional, Katsuma, A., additional, Imai, E., additional, Shibata, M., additional, Tada, M., additional, Shimbo, T., additional, Kikuchi, Y., additional, Oka, S., additional, Muramatsu, T., additional, Yanagisawa, N., additional, Fukutake, K., additional, Yamamoto, Y., additional, Ajisawa, A., additional, Tsuchiya, K., additional, Nitta, K., additional, Ando, M., additional, Liang, X., additional, Wang, P., additional, Liu, Z., additional, Zhao, Z., additional, Luyckx, V., additional, Bowker, S., additional, Miekle, A., additional, Toth, E., additional, Heguilen, R., additional, Malvar, A., additional, Hermes, R., additional, Cohen, L., additional, Muguerza, G., additional, Lococo, B., additional, Bernasconi, A., additional, Loboda, O., additional, Dudar, I., additional, Krot, V., additional, Alekseeva, V., additional, Ichinose, M., additional, Sasagawa, N., additional, Toyama, K., additional, Saito, A., additional, Kayamori, Y., additional, Kang, D., additional, Kim, H. W., additional, Yoshioka, K., additional, Hara, M., additional, Ohashi, K., additional, Maksudova, A., additional, Khalfina, T., additional, Cuoghi, A., additional, Bellei, E., additional, Caiazzo, M., additional, Bergamini, S., additional, Palladino, G., additional, Monari, E., additional, Tomasi, A., additional, Loiacono, E., additional, Camilla, R., additional, Dapr, V., additional, Morando, L., additional, Gallo, R., additional, Peruzzi, L., additional, Conrieri, M., additional, Bianciotto, M., additional, Bosetti, F. M., additional, Coppo, R., additional, DI Lullo, L., additional, Floccari, F., additional, Rivera, R., additional, Granata, A., additional, Faiola, R., additional, Feliziani, C., additional, Villani, A., additional, Malaguti, M., additional, Santoboni, A., additional, Kyriaki, K., additional, Droulias, J., additional, Bogdanova, M., additional, Rameev, V. V., additional, Simonyan, A. H., additional, Kozlovskaya, L. V., additional, Altiparmak, M. R., additional, Trabulus, S., additional, Akalin, N., additional, Yalin, A. S., additional, Esenkaya, A., additional, Yalin, S. F., additional, Serdengeae(C), K., additional, Arita, D., additional, Cunha, T., additional, Perez, J., additional, Sakata, M., additional, Arita, L., additional, Nogueira, M., additional, Jara, Z., additional, Souza, N., additional, Casarini, D., additional, Metzger, M., additional, Vallet, M., additional, Karras, A., additional, Froissart, M., additional, Stengel, B., additional, Houillier, P., additional, Paul, K., additional, Kretzschmar, D., additional, Yilmaz, A., additional, Ba hlein, B., additional, Titze, S., additional, Figulla, H.-R., additional, Wolf, G., additional, Busch, M., additional, Korotchaeva, Y., additional, Gordovskaya, N., additional, Kozlovskaya, L., additional, Ng, K. P., additional, Sharma, P., additional, Stringer, S., additional, Jesky, M., additional, Dutton, M., additional, Ferro, C., additional, Cockwell, P., additional, Moon, S. J., additional, Lee, S. C., additional, Yoon, S. Y., additional, Lee, J. E., additional, Han, S. J., additional, Anna, B., additional, Kirsch, T., additional, Svjetlana, L., additional, Joon-Keun, P., additional, Jan, B., additional, Johanna, K., additional, Haller, H., additional, Haubitz, M., additional, Smirnov, A., additional, Kayukov, I., additional, Rafrafi, N., additional, Degtereva, O., additional, Dobronravov, V., additional, Koch, M., additional, Stefan, H., additional, Dika, G., additional, Antoine, M.-H., additional, Husson, C., additional, Kos, J., additional, Milic, M., additional, Fucek, M., additional, Cvoriocec, D., additional, Bourgeade, M.-F., additional, Nortier, J. L., additional, Jelakovic, B., additional, Nawal, E. H., additional, Naoufal, M., additional, Nabila, M., additional, Fadwa, E. M., additional, Salma, E. K., additional, Nisrine, B., additional, Mohamed, Z., additional, Guislaine, M., additional, Mohamed Gharbi, B., additional, Benyounes, R., additional, Sotila, G. G., additional, Sorin, R., additional, Irina Magdalena, D., additional, Roxana, C., additional, Claudia, R., additional, Correa Barcellos, F., additional, Hallal, P. H., additional, Bohlke, M., additional, Boscolo Del Vechio, F., additional, Reges, A., additional, Santos, I., additional, Mielke, G., additional, Fortes, M., additional, Antunez, B., additional, Laganovic, M., additional, Vukovic Lela, I., additional, Karanovic, S., additional, Seric, J., additional, Premuic, V., additional, Fitrek, M., additional, Fodor, L., additional, Meljkovic Vrkic, T., additional, Bansal, V., additional, Hoppensteadt, D., additional, and Fareed, J., additional more...
- Published
- 2012
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Catalog
3. Protein C and protein S deficiencies may be related to survival among hemodialysis patients.
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Ichinose M, Sasagawa N, Chiba T, Toyama K, Kayamori Y, and Kang D
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- Aged, Female, Follow-Up Studies, Humans, Kidney Failure, Chronic blood, Male, Middle Aged, Protein C Deficiency blood, Protein S Deficiency blood, Protein S Deficiency therapy, Renal Dialysis trends, Survival Rate trends, Kidney Failure, Chronic mortality, Kidney Failure, Chronic therapy, Protein C Deficiency mortality, Protein S Deficiency mortality, Renal Dialysis mortality
- Abstract
Background: Thrombophilia due to protein C (PC) and protein S (PS) deficiencies is highly prevalent among patients with stage 5 chronic kidney disease and is reported to arise due to extracorporeal circulation during hemodialysis (HD). This study aimed to evaluate the relationship between HD treatment and thrombophilia., Methods: A total of 114 Japanese patients on maintenance HD (62 men, 52 women) were followed during 2008-2011. Their survival rates were compared against the duration of HD. Prior to each HD, coagulation/fibrinolysis parameters and PC and PS activities were measured using standard techniques. The patients were divided into two groups: Group 1, with PC and/or PS deficiencies (n = 32), and Group 2, without PC and PS deficiencies (n = 82). The influence of such deficiencies and duration of dialysis on survival was examined. Time-to-event analysis was applied using Kaplan-Meier estimates, and the log-rank test was proposed to test the equivalence of relative survival data. Hazard ratios and 95% confidence intervals (CI) were calculated., Results: Of the 114 patients, 37 died (Group 1, 22; Group 2, 15). The hazard ratio (95% CI) was higher (p = 0.004) in Group 1 than Group 2. Gene analyses of PC and PS were performed in 14 patients from Group 1. No mutations in either protein were observed. We analyzed the causes of death in both groups; however, the estimated thrombophilia-related incidence of death could not be determined due to small sample size of HD patients., Conclusions: Our results suggest that PC and PS deficiencies may be related to survival in HD patients. However, this finding warrants additional research. more...
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- 2019
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4. Complete remission of human parvovirus b19 associated symptoms by loxoprofen in patients with atopic predispositions.
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Kazama I, Sasagawa N, and Nakajima T
- Abstract
Two cases of women in their thirties with past histories of atopic dermatitis and allergic rhinitis developed a low grade fever, followed by a butterfly-shaped erythema, swelling of their fingers, and polyarthralgia. Despite such symptoms that overlap with those of systemic lupus erythematosus (SLE), the diagnostic criteria for SLE were not fulfilled. Due to positive results for human parvovirus B19 (HPV-B19) IgM antibodies in the serum, diagnoses of HPV-B19 infection were made in both cases. Although acetaminophen failed to improve their deteriorating symptoms, a nonsteroidal anti-inflammatory drug (NSAID), loxoprofen, completely removed the symptoms immediately after the administration. In those cases, since the patients were predisposed to atopic disorders, an increased immunological response based on the lymphocyte hypersensitivity was likely to be involved in the pathogenesis. The immunomodulatory property of NSAID was thought to repress such lymphocyte activity and thus provided a rapid and sustained remission of the disease. more...
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- 2012
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5. Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1.
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Koebis M, Ohsawa N, Kino Y, Sasagawa N, Nishino I, and Ishiura S
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- Base Sequence, CELF1 Protein, Connectin, Consensus Sequence, Exons, HEK293 Cells, Humans, Molecular Sequence Data, Muscle, Skeletal metabolism, Mutation genetics, Myotonic Dystrophy metabolism, RNA Splice Sites, RNA-Binding Proteins metabolism, Alternative Splicing genetics, Gene Expression Regulation, Muscle Proteins genetics, Myotonic Dystrophy genetics
- Abstract
Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by a CTG repeat expansion in the 3'-UTR of dystrophia myotonica-protein kinase. Aberrant regulation of alternative splicing is a characteristic feature of DM. Dozens of genes have been found to be abnormally spliced; however, few reported splicing abnormalities explain the phenotypes of DM1 patients. Thus, we hypothesized that other, unknown abnormal splicing events exist. Here, by using exon array, we identified aberrant inclusion of myomesin 1 (MYOM1) exon 17a as a novel splicing abnormality in DM1 muscle. A cellular splicing assay with a MYOM1 minigene revealed that not only MBNL1-3 but also CELF1 and 2 decreased the inclusion of MYOM1 exon 17a in HEK293T cells. Expression of expanded CUG repeat impeded MBNL1 activity but did not affect CELF1 activity on the splicing of MYOM1 minigene. Our results suggest that the downregulation of MBNL proteins should lead to the abnormal splicing of MYOM1 exon 17a in DM1 muscle., (© 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.) more...
- Published
- 2011
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6. Transgenic rice expressing amyloid β-peptide for oral immunization.
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Yoshida T, Kimura E, Koike S, Nojima J, Futai E, Sasagawa N, Watanabe Y, and Ishiura S
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- Agrobacterium tumefaciens genetics, Amyloid beta-Peptides genetics, Amyloid beta-Peptides immunology, Animals, Antibodies blood, Enzyme-Linked Immunosorbent Assay, Mice, Peptide Fragments genetics, Peptide Fragments immunology, Transformation, Bacterial, Vaccines, Edible therapeutic use, Alzheimer Disease immunology, Amyloid beta-Peptides therapeutic use, Immunotherapy, Active methods, Oryza genetics, Peptide Fragments therapeutic use, Plants, Genetically Modified metabolism
- Abstract
Various vaccine therapies for Alzheimer's disease (AD) have been investigated. Here we report transgenic rice expressing amyloid β-peptide (Aβ). The Aβ42 gene fused with a green fluorescent protein gene was introduced into rice using the Agrobacterium method. When transgenic brown rice expressing Aβ was orally administered to mice, serum anti-Aβ antibody titers were elevated. The same results were observed when mice were fed boiled, transgenic brown rice. The results indicate that an edible vaccine against AD using rice may be feasible. A vaccine derived from rice would be far cheaper than existing medical vaccines., (© Ivyspring International Publisher.) more...
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- 2011
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7. Production of anti-amyloid β antibodies in mice fed rice expressing amyloid β.
- Author
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Nojima J, Ishii-Katsuno R, Futai E, Sasagawa N, Watanabe Y, Yoshida T, and Ishiura S
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- Administration, Oral, Alzheimer Disease immunology, Alzheimer Disease prevention & control, Alzheimer Disease therapy, Amyloid beta-Peptides chemistry, Amyloid beta-Peptides genetics, Animals, Antibody Specificity immunology, Epitope Mapping, Female, Gene Expression, Male, Mice, Plants, Genetically Modified genetics, Th2 Cells immunology, Vaccines, Edible administration & dosage, Vaccines, Edible chemistry, Vaccines, Edible genetics, Amyloid beta-Peptides administration & dosage, Amyloid beta-Peptides immunology, Antibodies immunology, Oryza genetics, Vaccines, Edible immunology
- Abstract
The main signs of Alzheimer's disease (AD) are cognitive impairment and senile plaques composed of amyloid beta (Aβ) observed in patients' brains. Therefore, therapy for AD focuses on the removal of Aβ. We developed an "edible vaccine" that employs intestinal immunity with little to no side effects. Rice was utilized as an edible vaccine. It expressed GFP-Aβ42. Aβ rice was administered orally to wild-type (WT) mice causing production of anti-Aβ antibodies. Since Aβ rice was mixed with the cholera toxin B subunit (CTB), antibody against the rice seed protein was also produced. Then, mice were caused to develop immune tolerance against the rice seed protein by oral administration of Aβ rice mixed with CTB. The results indicated that only anti-Aβ antibodies were produced. more...
- Published
- 2011
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8. MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1.
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Kino Y, Washizu C, Oma Y, Onishi H, Nezu Y, Sasagawa N, Nukina N, and Ishiura S
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- Animals, CELF Proteins, Chloride Channels metabolism, DNA Repeat Expansion, Exons, Humans, Mice, Muscle, Skeletal metabolism, RNA Splice Sites, RNA, Messenger metabolism, RNA-Binding Proteins antagonists & inhibitors, Alternative Splicing, Chloride Channels genetics, RNA-Binding Proteins metabolism
- Abstract
The expression and function of the skeletal muscle chloride channel CLCN1/ClC-1 is regulated by alternative splicing. Inclusion of the CLCN1 exon 7A is aberrantly elevated in myotonic dystrophy (DM), a genetic disorder caused by the expansion of a CTG or CCTG repeat. Increased exon 7A inclusion leads to a reduction in CLCN1 function, which can be causative of myotonia. Two RNA-binding protein families--muscleblind-like (MBNL) and CUG-BP and ETR-3-like factor (CELF) proteins--are thought to mediate the splicing misregulation in DM. Here, we have identified multiple factors that regulate the alternative splicing of a mouse Clcn1 minigene. The inclusion of exon 7A was repressed by MBNL proteins while promoted by an expanded CUG repeat or CELF4, but not by CUG-BP. Mutation analyses suggested that exon 7A and its flanking region mediate the effect of MBNL1, whereas another distinct region in intron 6 mediates that of CELF4. An exonic splicing enhancer essential for the inclusion of exon 7A was identified at the 5' end of this exon, which might be inhibited by MBNL1. Collectively, these results provide a mechanistic model for the regulation of Clcn1 splicing, and reveal novel regulatory properties of MBNL and CELF proteins. more...
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- 2009
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9. Polyalanine tracts directly induce the release of cytochrome c, independently of the mitochondrial permeability transition pore, leading to apoptosis.
- Author
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Toriumi K, Oma Y, Mimoto A, Futai E, Sasagawa N, Turk B, and Ishiura S
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- Animals, COS Cells ultrastructure, Caspase 3 metabolism, Chlorocebus aethiops, Enzyme Activation, Humans, Mice, Mitochondria, Liver enzymology, Mitochondria, Liver metabolism, Mitochondrial Permeability Transition Pore, Apoptosis physiology, Cytochromes c metabolism, Mitochondria enzymology, Mitochondria metabolism, Mitochondrial Membrane Transport Proteins metabolism, Peptides metabolism, Peptides pharmacology
- Abstract
In recent years, several novel types of disorder caused by the expansion of triplet repeats in specific genes have been characterized; in the "polyalanine diseases", these expanded repeats result in proteins with aberrantly elongated polyalanine tracts. In this study, we fused expanded polyalanine tracts to yellow fluorescent protein to examine their physical interaction with mitochondria. Tracts containing more than 23 alanine repeats were found to physically associate with mitochondria, strongly suggesting that an interaction between polyalanine tracts and mitochondria is a contributing factor in the pathology of polyalanine diseases. Furthermore, in in vitro experiments, polyalanine tracts induced release of cytochrome c from mitochondria and caspase-3 activation, independently of the mitochondrial permeability transition pore. These results suggest that oligomerized polyalanine tracts might induce the rupture of the mitochondrial membrane, the subsequent release of cytochrome c, and apoptosis. This novel mechanism for polyalanine tract cytotoxicity might be common to the pathogenesis of all polyalanine diseases. Further investigation of this mechanism might aid the development of therapies for these diseases. more...
- Published
- 2009
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10. Dysbindin-1, a schizophrenia-related protein, functionally interacts with the DNA- dependent protein kinase complex in an isoform-dependent manner.
- Author
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Oyama S, Yamakawa H, Sasagawa N, Hosoi Y, Futai E, and Ishiura S
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- Carrier Proteins genetics, Carrier Proteins physiology, Cell Nucleus, Central Nervous System, Dysbindin, Dystrophin-Associated Proteins, Humans, Phosphorylation, Polymorphism, Single Nucleotide, Protein Isoforms metabolism, Carrier Proteins metabolism, DNA-Activated Protein Kinase metabolism, Schizophrenia etiology
- Abstract
DTNBP1 has been recognized as a schizophrenia susceptible gene, and its protein product, dysbindin-1, is down-regulated in the brains of schizophrenic patients. However, little is known about the physiological role of dysbindin-1 in the central nervous system. We hypothesized that disruption of dysbindin-1 with unidentified proteins could contribute to pathogenesis and the symptoms of schizophrenia. GST pull-down from human neuroblastoma lysates showed an association of dysbindin-1 with the DNA-dependent protein kinase (DNA-PK) complex. The DNA-PK complex interacts only with splice isoforms A and B, but not with C. We found that isoforms A and B localized in nucleus, where the kinase complex exist, whereas the isoform C was found exclusively in cytosol. Furthermore, results of phosphorylation assay suggest that the DNA-PK complex phosphorylated dysbindin-1 isoforms A and B in cells. These observations suggest that DNA-PK regulates the dysbindin-1 isoforms A and B by phosphorylation in nucleus. Isoform C does not contain exons from 1 to 6. Since schizophrenia-related single nucleotide polymorphisms (SNPs) occur in these introns between exon 1 and exon 6, we suggest that these SNPs might affect splicing of DTNBP1, which leads to impairment of the functional interaction between dysbindin-1 and DNA-PK in schizophrenic patients. more...
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- 2009
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11. Endoplasmic reticulum stress caused by aggregate-prone proteins containing homopolymeric amino acids.
- Author
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Uchio N, Oma Y, Toriumi K, Sasagawa N, Tanida I, Fujita E, Kouroku Y, Kuroda R, Momoi T, and Ishiura S
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- Amino Acids analysis, Animals, Bacterial Proteins metabolism, Cells, Cultured, Hydrophobic and Hydrophilic Interactions, Leucine metabolism, Luminescent Proteins metabolism, Mice, Microscopy, Fluorescence, Peptides chemistry, Peptides metabolism, Proteasome Endopeptidase Complex metabolism, Transfection, Ubiquitin metabolism, Amino Acids chemistry, Endoplasmic Reticulum physiology
- Abstract
Many human proteins have homopolymeric amino acid (HPAA) tracts, but their physiological functions or cellular effects are not well understood. Previously, we expressed 20 HPAAs in mammalian cells and showed characteristic intracellular localization, in that hydrophobic HPAAs aggregated strongly and caused high cytotoxicity in proportion to their hydrophobicity. In the present study, we investigated the cytotoxicity of these aggregate-prone hydrophobic HPAAs, assuming that the ubiquitin proteasome system is impaired in the same manner as other well-known aggregate-prone polyglutamine-containing proteins. Some highly hydrophobic HPAAs caused a deficiency in the ubiquitin proteasome system and excess endoplasmic reticulum stress, leading to apoptosis. These results indicate that the property of causing excess endoplasmic reticulum stress by proteasome impairment may contribute to the strong cytotoxicity of highly hydrophobic HPAAs, and proteasome impairment and the resulting excess endoplasmic reticulum stress is not a common cytotoxic effect of aggregate-prone proteins such as polyglutamine. more...
- Published
- 2007
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12. Interactions between homopolymeric amino acids (HPAAs).
- Author
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Oma Y, Kino Y, Toriumi K, Sasagawa N, and Ishiura S
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- Animals, COS Cells, Chlorocebus aethiops, Hydrophobic and Hydrophilic Interactions, Proteins analysis, Proteins chemistry, Two-Hybrid System Techniques, Peptides chemistry, Repetitive Sequences, Amino Acid
- Abstract
Many human proteins contain consecutive amino acid repeats, known as homopolymeric amino acid (HPAA) tracts. Some inherited diseases are caused by proteins in which HPAAs are expanded to an excessive length. To this day, nine polyglutamine-related diseases and nine polyalanine-related diseases have been reported, including Huntington's disease and oculopharyngeal muscular dystrophy. In this study, potential HPAA-HPAA interactions were examined by yeast two-hybrid assays using HPAAs of approximately 30 residues in length. The results indicate that hydrophobic HPAAs interact with themselves and with other hydrophobic HPAAs. Previously, we reported that hydrophobic HPAAs formed large aggregates in COS-7 cells. Here, those HPAAs were shown to have significant interactions with each other, suggesting that hydrophobicity plays an important role in aggregation. Among the observed HPAA-HPAA interactions, the Ala28-Ala29 interaction was notable because polyalanine tracts of these lengths have been established to be pathogenic in several polyalanine-related diseases. By testing several constructs of different lengths, we clarified that polyalanine self-interacts at longer lengths (>23 residues) but not at shorter lengths (six to approximately 23 residues) in a yeast two-hybrid assay and a GST pulldown assay. This self-interaction was found to be SDS sensitive in SDS-PAGE and native-PAGE assays. Moreover, the intracellular localization of these long polyalanine tracts was also observed to be disturbed. Our results suggest that long tracts of polyalanine acquire SDS-sensitive self-association properties, which may be a prerequisite event for their abnormal folding. The misfolding of these tracts is thought to be a common molecular aspect underlying the pathogenesis of polyalanine-related diseases. more...
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- 2007
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13. Intracellular localization of homopolymeric amino acid-containing proteins expressed in mammalian cells.
- Author
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Oma Y, Kino Y, Sasagawa N, and Ishiura S
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- Animals, Bacterial Proteins genetics, COS Cells, Chlorocebus aethiops, Genes, Reporter, Genome, Human, Humans, Intracellular Space, Luminescent Proteins genetics, Peptides metabolism, Proteins chemistry, Proteins metabolism, Transfection, Peptides chemistry
- Abstract
Many human proteins have homopolymeric amino acid (HPAA) tracts, which are involved in protein-protein interactions and also have intrinsic polymerization properties. Polyglutamine or polyalanine expansions cause several neurodegenerative diseases. To examine the properties of HPAAs, we expressed 20 kinds of 30-residue HPAA fused to the C terminus of yellow fluorescent protein in mammalian cells. Specific localization was observed depending on the HPAA. Polyarginine and polylysine aggregated in the nucleus. Polyalanine, polyhistidine, polyisoleucine, polyleucine, polymethionine, polyphenylalanine, polythreonine, polytryptophan, and polyvaline localized in the cytoplasm, and some of these HPAAs formed aggregate(s). Hydrophobic HPAAs such as polyisoleucine, polyleucine, polyphenylalanine, and polyvaline were found as one major aggregate or cumulus in the perinuclear region. Western blot analysis indicated that hydrophobic HPAA tracts appear to oligomerize and form high molecular weight complexes. These results indicate that hydrophobicity itself may trigger the oligomerization and aggregation of proteins when overexpressed in cells. Our experiments provide novel insights into the nature of the HPAAs that are often seen in human and other organisms. more...
- Published
- 2004
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14. Regulation of exocytosis through Ca2+/ATP-dependent binding of autophosphorylated Ca2+/calmodulin-activated protein kinase II to syntaxin 1A.
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Ohyama A, Hosaka K, Komiya Y, Akagawa K, Yamauchi E, Taniguchi H, Sasagawa N, Kumakura K, Mochida S, Yamauchi T, and Igarashi M
- Subjects
- Adenosine Triphosphate metabolism, Animals, Antigens, Surface chemistry, Brain Chemistry, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinases chemistry, Catalysis, Cells, Cultured, Chelating Agents pharmacology, Chromaffin Cells cytology, Chromaffin Cells drug effects, Chromaffin Cells metabolism, Exocytosis drug effects, Macromolecular Substances, Membrane Glycoproteins chemistry, Membrane Glycoproteins metabolism, Membrane Proteins chemistry, Membrane Proteins metabolism, Munc18 Proteins, Nerve Tissue Proteins chemistry, Neurons cytology, Neurons drug effects, Peptide Fragments pharmacology, Phosphoric Monoester Hydrolases pharmacology, Phosphorylation, Presynaptic Terminals metabolism, Protein Binding drug effects, Protein Binding physiology, Protein Structure, Tertiary physiology, Rats, SNARE Proteins, Superior Cervical Ganglion, Synaptosomal-Associated Protein 25, Synaptosomes chemistry, Synaptosomes metabolism, Synaptotagmins, Syntaxin 1, Antigens, Surface metabolism, Calcium metabolism, Calcium-Binding Proteins, Calcium-Calmodulin-Dependent Protein Kinases metabolism, Exocytosis physiology, Nerve Tissue Proteins metabolism, Neurons metabolism, Vesicular Transport Proteins
- Abstract
Syntaxin 1A/HPC-1 is a key component of the exocytotic molecular machinery, namely, the soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor mechanism. Although >10 syntaxin-binding proteins have been identified, they cannot completely explain the regulation of exocytosis. Thus, novel proteins may interact with syntaxin. Because exocytosis requires both Ca2+ and ATP, we searched for Ca2+/ATP-dependent syntaxin-binding proteins from the rat brain and discovered Ca2+/calmodulin-activated protein kinase II (CaMKII)-alpha. At Ca2+ concentrations of >10(-6) m, only autophosphorylated CaMKII bound to syntaxin. Bound CaMKII was released from syntaxin by EGTA or by phosphatase, indicating that the binding is reversible. CaMKII bound to the linker domain of syntaxin, unlike any other known syntaxin-binding proteins. CaMKII-syntaxin complexes were also detected in synaptosomes by immunoprecipitation, and when reconstituted in vitro, they recruited larger amounts of synaptotagmin and SNAP-25 than syntaxin alone. The microinjected CaMKII-binding domain of syntaxin specifically affected exocytosis in chromaffin cells and in neurons. These results indicate that the Ca2+/ATP-dependent binding of CaMKII to syntaxin is an important process in the regulation of exocytosis. more...
- Published
- 2002
- Full Text
- View/download PDF
15. Novel isoform of myotonin protein kinase: gene product of myotonic dystrophy is localized in the sarcoplasmic reticulum of skeletal muscle.
- Author
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Shimokawa M, Ishiura S, Kameda N, Yamamoto M, Sasagawa N, Saitoh N, Sorimachi H, Ueda H, Ohno S, Suzuki K, and Kobayashi T
- Subjects
- Actins analysis, Adult, Amino Acid Sequence, Blotting, Western, Cells, Cultured, Gene Expression Regulation, Developmental, Humans, Isoenzymes genetics, Microscopy, Immunoelectron, Molecular Sequence Data, Muscle Development, Muscle, Skeletal growth & development, Muscle, Skeletal ultrastructure, Myosins analysis, Myotonic Dystrophy genetics, Myotonic Dystrophy pathology, Myotonin-Protein Kinase, Protein Kinases genetics, Sarcoplasmic Reticulum ultrastructure, Isoenzymes metabolism, Muscle, Skeletal enzymology, Myotonic Dystrophy enzymology, Protein Kinases metabolism, Protein Serine-Threonine Kinases, Sarcoplasmic Reticulum enzymology
- Abstract
It is quite important to know the exact localization and function of myotonin protein kinase (MtPK), identified as the gene product of myotonic dystrophy, the most prevalent disease with multisystem disorders among muscular dystrophies. To investigate the localization of MtPK, we raised a polyclonal antibody against a synthetic peptide chosen within the deduced sequence of MtPK. This antibody detected both a membrane-bound 70-kd protein and a soluble 55-kd protein on Western blots of human muscles. By using this antibody for immunohistochemical studies of both biopsied human skeletal muscle fibers and mature innervated cultured muscle fibers, we can now demonstrate by confocal laser scanning microscopy that MtPK is localized mainly in the I-band. By immunoelectron microscopy, it was determined that MtPK is a membrane-bound protein localized mainly in the terminal cisternae of the sarcoplasmic reticulum. To our knowledge, this is the first documentation of the ultrastructural localization of MtPK. This finding is quite important for clarifying the pathophysiological basis of myotonic dystrophy, which might be due to a dysregulation of calcium metabolism. more...
- Published
- 1997
16. Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence.
- Author
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Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, and Maruyama K
- Subjects
- Amino Acid Sequence, Animals, Binding Sites, Cell Line, Connectin, Humans, Hydrolysis, Molecular Sequence Data, Rabbits, Rats, Calpain metabolism, Membrane Proteins metabolism, Muscle Proteins metabolism, Muscle, Skeletal metabolism, Muscular Dystrophies metabolism, Protein Kinases metabolism
- Abstract
p94, a muscle-specific member of calpain family, is unique in that it undergoes rapid and exhaustive autolysis with a half-life of less than 1 h resulting in its disappearance from muscle. Recently, p94 was shown to be responsible for limb girdle muscular dystrophy type 2A. To elucidate the muscular proteolytic system mediated by p94 and to solve the mystery of its unusually rapid autolysis, we searched for p94-binding proteins by the two-hybrid system. Although calpain small subunit plays a crucial role for regulation of ubiquitous calpains, it did not associate with p94. After a screening of skeletal muscle library, connectin (or titin), a gigantic filamentous protein spanning the M- to Z-lines of muscle sarcomere, was found to bind to p94 through a p94-specific region, IS2. The connectin-insoluble fraction of washed myofibrils contained full-length intact p94, suggesting that connectin regulates p94 activity. more...
- Published
- 1995
- Full Text
- View/download PDF
17. Expression of a novel human myotonin protein kinase (MtPK) cDNA clone which encodes a protein with a thymopoietin-like domain in COS cells.
- Author
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Sasagawa N, Sorimachi H, Maruyama K, Arahata K, Ishiura S, and Suzuki K
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Blotting, Western, Cell Line, Cloning, Molecular, DNA, Complementary, Humans, Molecular Sequence Data, Myotonin-Protein Kinase, Protein Kinases chemistry, Rats, Sequence Homology, Amino Acid, Protein Kinases genetics, Protein Serine-Threonine Kinases, Thymopoietins chemistry
- Abstract
A full-length cDNA of human myotonin protein kinase (MtPK) was cloned and expressed in COS-1 cells. MtPK is recovered from the cytosolic fraction of the COS extract as a 70 kDa protein, which coincides with the size deduced from the predicted amino acid sequence. The sequence has a significant homology to thymopoietin, a peptide hormone of the thymus. Biochemical characteristics of MtPK expressed in COS-1 cells and its expression in rat tissues are investigated. more...
- Published
- 1994
- Full Text
- View/download PDF
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