Updated on 2024/02/01

写真a

 
YAMAMOTO Yumiko
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
External link

Degree

  • (BLANK) ( Okayama University )

  • (BLANK) ( Okayama University )

Research Interests

  • Clostridium botulinum

  • Neurotoxin

  • 神経毒素

  • ボツリヌス菌

Research Areas

  • Life Science / Bacteriology

  • Life Science / Molecular biology

  • Life Science / Functional biochemistry

 

Papers

  • Mechanism and clinical use of botulinum neurotoxin in head and facial region Reviewed

    Swarnalakshmi Raman, Yumiko Yamamoto, Yoshitaka Suzuki, Yoshizo Matsuka

    Journal of Prosthodontic Research   67 ( 4 )   493 - 505   2023.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Prosthodontic Society  

    DOI： 10.2186/jpr.jpr_d_22_00238

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  • Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model Reviewed

    Arief Waskitho, Yumiko Yamamoto, Swarnalakshmi Raman, Fumiya Kano, Huijiao Yan, Resmi Raju, Shaista Afroz, Tsuyoshi Morita, Daisuke Ikutame, Kazuo Okura, Masamitsu Oshima, Akihito Yamamoto, Otto Baba, Yoshizo Matsuka

    Toxins   13 ( 10 )   704 - 704   2021.10

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Peripheral nerve injury leads to sensory ganglion hyperexcitation, which increases neurotransmitter release and neuropathic pain. Botulinum toxin type A (BoNT/A) regulates pain transmission by reducing neurotransmitter release, thereby attenuating neuropathic pain. Despite multiple studies on the use of BoNT/A for managing neuropathic pain in the orofacial region, its exact mechanism of transport remains unclear. In this study, we investigated the effects of BoNT/A in managing neuropathic pain in two different animal models and its transport mechanism in the trigeminal nerve. Intraperitoneal administration of cisplatin induced bilateral neuropathic pain in the orofacial region, reducing the head withdrawal threshold to mechanical stimulation. Unilateral infraorbital nerve constriction (IONC) also reduced the ipsilateral head withdrawal threshold to mechanical stimulation. Unilateral peripheral administration of BoNT/A to the rat whisker pad attenuated cisplatin-induced pain behavior bilaterally. Furthermore, contralateral peripheral administration of BoNT/A attenuated neuropathy-induced behavior caused by IONC. We also noted the presence of BoNT/A in the blood using the mouse bioassay. In addition, the Alexa Fluor-488-labeled C-terminal half of the heavy chain of BoNT/A (BoNT/A-Hc) was localized in the neurons of the bilateral trigeminal ganglia following its unilateral administration. These findings suggest that axonal and hematogenous transport are involved in the therapeutic effects of peripherally administered BoNT/A in the orofacial region.

    DOI： 10.3390/toxins13100704

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  • Elizabethkingia anophelis, an emerging pathogen, inhibits RAW 264.7 macrophage function Reviewed

    I Putu Bayu Mayura, Kazuyoshi Gotoh, Hayato Nishimura, Erina Nakai, Takehiko Mima, Yumiko Yamamoto, Kenji Yokota, Osamu Matsushita

    Microbiology and Immunology   65 ( 8 )   317 - 324   2021.8

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Elizabethkingia anophelis is a pathogen that can cause a life-threatening infection in immunocompromised patients. The first case of E. anophelis infection was reported in 2013; subsequently, an increase in its incidence has been reported globally. Additionally, a mortality rate of more than 30% was observed in the US outbreak of 2015. To date, the pathogenic mechanisms underlying E. anophelis infection, such as toxin production, remain unclear. Since tissue macrophages act as the first line of defense against pathogens, in the present study the interactions between E. anophelis and a macrophage-like cell line RAW 264.7 were examined. Although E. anophelis showed no cytotoxicity toward RAW 264.7 macrophages, the infection inhibited LPS-induced morphological changes and activation of differentiation markers for the polarization of RAW 264.7 macrophages toward an M1-like phenotype. However, when the cell contact was restricted using Transwell inserts or bacterial culture supernatants were used instead of live bacteria, no such inhibition was observed. Moreover, it was shown that E. anophelis evaded phagocytosis. Overall, the results suggest that E. anophelis infection inhibits the differentiation of RAW 264.7 macrophages to a pro-inflammatory phenotype in a contact-dependent manner.

    DOI： 10.1111/1348-0421.12888

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1348-0421.12888

  • Environmental survey of Methicillin-Resistant Staphylococci in a Hospital in Japan Reviewed

    AKARI WATANABE, TOKIKO WATANABE, SUSUMU KOKEGUCHI, YUMIKO YAMAMOTO, OSAMU MATSUSHITA, KENJI YOKOTA

    Biocontrol Science   26 ( 3 )   137 - 145   2021

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    Publishing type：Research paper (scientific journal)   Publisher：The Society for Antibacterial and Antifungal Agents, Japan  

    DOI： 10.4265/bio.26.137

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  • Analysis of a plasmid encoding botulinum neurotoxin type G gene in Clostridium argentinense Reviewed

    Yoshihiko Sakaguchi, Jumpei Uchiyama, Akira Také, Kazuyoshi Gotoh, Masakiyo Sakaguchi, Tomonori Suzuki, Yumiko Yamamoto, Koji Hosomi, Tomoko Kohda, Masafumi Mukamoto, Shunji Kozaki, Shunji Hayashi, Keiji Oguma

    Anaerobe   66   102281 - 102281   2020.12

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.anaerobe.2020.102281

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  • Vibrio alginolyticus VepA Induces Lysosomal Membrane Permeability and Cathepsin-Independent Cell Death. Reviewed

    Agus Eka Darwinata, Kazuyoshi Gotoh, Takehiko Mima, Yumiko Yamamoto, Kenji Yokota, Osamu Matsushita

    Acta Medica Okayama   72 ( 3 )   231 - 239   2018.6

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    The bacterium Vibrio alginolyticus, an opportunistic pathogen in humans, has a type III secretion system (T3SS) that is responsible for its cytotoxicity toward eukaryotic cells. The effector of T3SS that is responsible for the cytotoxicity had not been identified. Here we demonstrate that VepA, a homolog of the T3SS effector in V. parahaemolyticus, is required for cytotoxicity in V. alginolyticus. VepA induces lysosomal membrane permeabilization, and it allows the leakage of only small molecules into the cytosol. Our findings revealed that VepA induces cathepsin-independent cell death in mammalian cells. The ferrous ion, one of the small molecules in the lysosome contents, appears to be involved in the cell death caused by V. alginolyticus VepA.

    DOI： 10.18926/AMO/56068

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  • Expression of Collagenase is Regulated by the VarS/VarA Two-Component Regulatory System in Vibrio alginolyticus Reviewed

    Takehiko Mima, Kazuyoshi Gotoh, Yumiko Yamamoto, Keiko Maeda, Taku Shirakawa, Shunsuke Matsui, Yumi Murata, Takaki Koide, Hiroshi Tokumitsu, Osamu Matsushita

    The Journal of Membrane Biology   251 ( 1 )   51 - 63   2018.2

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1007/s00232-017-9991-9

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    Other Link： http://link.springer.com/content/pdf/10.1007/s00232-017-9991-9.pdf

  • Botulinum neurotoxin type A alleviates mechanical hypersensitivity associated with infraorbital nerve constriction injury in rats Reviewed

    Noboru Noma, Kosuke Watanabe, Yuka Sato, Yoshiki Imamura, Yumiko Yamamoto, Reio Ito, Mitsuru Maruno, Kohei Shimizu, Koichi Iwata

    Neuroscience Letters   637   96 - 101   2017.1

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.neulet.2016.11.043

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  • Cross-Excitation in Peripheral Sensory Ganglia Associated with Pain Transmission Reviewed

    Katsuhiro Omoto, Kotaro Maruhama, Ryuji Terayama, Yumiko Yamamoto, Osamu Matsushita, Tomosada Sugimoto, Keiji Oguma, Yoshizo Matsuka

    Toxins   7 ( 8 )   2906 - 2917   2015.8

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    DOI： 10.3390/toxins7082906

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  • Genomics of Clostridium botulinum group III strains Reviewed

    Yoshihiko Sakaguchi, Tomonori Suzuki, Yumiko Yamamoto, Atsushi Nishikawa, Keiji Oguma

    Research in Microbiology   166 ( 4 )   318 - 325   2015.5

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.resmic.2014.07.016

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  • Phospholipase C Produced by Clostridium botulinum Types C and D: Comparison of Gene, Enzymatic, and Biological Activities with Those of Clostridium perfringens Alpha-toxin Reviewed

    Ni Nengah Dwi Fatmawati, Yoshihiko Sakaguchi, Tomonori Suzuki, Masataka Oda, Kenta Shimizu, Yumiko Yamamoto, Jun Sakurai, Osamu Matsushita, Keiji Oguma

    Acta Medica Okayama   67 ( 1 )   9 - 18   2013.2

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    Language：English   Publisher：Okayama University Medical School  

    DOI： 10.18926/AMO/49252

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    Other Link： http://search.jamas.or.jp/link/ui/2013249132

  • Intraprostatic Botulinum Neurotoxin Type A Injection for Benign Prostatic Hyperplasia: Preliminary Results with a Newly Purified Neurotoxin Reviewed

    Teruhiko Yokoyama, Yumiko Yamamoto, Tomonori Suzuki, Keiji Oguma, Atsushi Nagai

    Acta Medica Okayama   66 ( 4 )   291 - 297   2012.8

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

    DOI： 10.18926/AMO/48668

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    Other Link： http://search.jamas.or.jp/link/ui/2013306579

  • Clostridium botulinum Type E Toxins Bind to Caco-2 Cells by a Different Mechanism from That of Type A Toxins Reviewed

    Zhang Kai, Yamamoto Yumiko, Suzuki Tomonori, Yokota Kenji, Ma Shaobo, Nengah Dwi Fatmawati Ni, Oguma Keiji

    Acta Medica Okayama   66 ( 3 )   253 - 261   2012.6

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

    DOI： 10.18926/AMO/48565

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    Other Link： http://search.jamas.or.jp/link/ui/2013156720

  • Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction-induced thermal hyperalgesia in an operant assay Reviewed

    A. KUMADA, Y. MATSUKA, I. SPIGELMAN, K. MARUHAMA, Y. YAMAMOTO, J. K. NEUBERT, T. A. NOLAN, K. WATANABE, K. MAEKAWA, H. KAMIOKA, T. YAMASHIRO, T. KUBOKI, K. OGUMA

    Journal of Oral Rehabilitation   39 ( 1 )   63 - 72   2012.1

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1111/j.1365-2842.2011.02236.x

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  • Application of Purified Botulinum Type A Neurotoxin to Treat Experimental Trigeminal Neuropathy in Rats and Patients with Urinary Incontinence and Prostatic Hyperplasia Reviewed

    Yoshizo Matsuka, Teruhiko Yokoyama, Yumiko Yamamoto, Tomonori Suzuki, Ni Nengah Dwi Fatmawati, Atsushi Nishikawa, Tohru Ohyama, Toshihiro Watanabe, Takuo Kuboki, Atsushi Nagai, Keiji Oguma

    Journal of Toxicology   2012   1 - 8   2012

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    Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

    Type A neurotoxin (NTX) of<italic>Clostridium botulinum</italic>was purified by a simple procedure using a lactose gel column. The toxicity of this purified toxin preparation was retained for at least 1 year at −30°C by supplementation with either 0.1% albumin or 0.05% albumin plus 1% trehalose. When purified NTX was used to treat 49 patients with urinary incontinence caused by either refractory idiopathic or neurogenic detrusor overactivity, 36 patients showed significant improvement in symptoms. These beneficial effects were also observed in cases of prostatic hyperplasia. The results obtained with NTX were similar to that of Botox. The effects of NTX on trigeminal neuralgia induced by infraorbital nerve constriction (IoNC) in rats were also studied. Trigeminal ganglion neurons from ipsilateral to IoNC exhibited significantly faster onset of FM4-64 release than sham-operated contralateral neurons. Intradermal injection of NTX in the area of IoNC alleviated IoNC-induced pain behavior and reduced the exaggerated FM4-64 release in trigeminal ganglion neurons.

    DOI： 10.1155/2012/648384

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    Other Link： http://downloads.hindawi.com/journals/jt/2012/648384.xml

  • Effects of Purified Newly Developed Botulinum Neurotoxin Type A in Rat Prostate Reviewed

    Yasuhiro Nishiyama, Teruhiko Yokoyama, Kazuhito Tomizawa, Kikuo Okamura, Yumiko Yamamoto, Hideki Matsui, Keiji Oguma, Atsushi Nagai, Hiromi Kumon

    Urology   74 ( 2 )   436 - 439   2009.8

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.urology.2009.01.047

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  • Knockdown of the PsbP protein does not prevent assembly of the dimeric PSII core complex but impairs accumulation of photosystem II supercomplexes in tobacco Reviewed

    Kunio Ido, Kentaro Ifuku, Yumiko Yamamoto, Seiko Ishihara, Akio Murakami, Keiji Takabe, Chikahiro Miyake, Fumihiko Sato

    Biochimica et Biophysica Acta (BBA) - Bioenergetics   1787 ( 7 )   873 - 881   2009.7

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.bbabio.2009.03.004

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  • Molecular Analysis of an Extrachromosomal Element Containing the C2 Toxin Gene Discovered in Clostridium botulinum Type C Reviewed

    Yoshihiko Sakaguchi, Tetsuya Hayashi, Yumiko Yamamoto, Keisuke Nakayama, Kai Zhang, Shaobo Ma, Hideyuki Arimitsu, Keiji Oguma

    Journal of Bacteriology   191 ( 10 )   3282 - 3291   2009.5

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    Publishing type：Research paper (scientific journal)   Publisher：American Society for Microbiology  

    <title>ABSTRACT</title>

    <italic>Clostridium botulinum</italic>
    cultures are classified into seven types, types A to G, based on the antigenicity of the neurotoxins produced. Of these seven types, only types C and D produce C2 toxin in addition to the neurotoxin. The C2 toxin consists of two components designated C2I and C2II. The genes encoding the C2 toxin components have been cloned, and it has been stated that they might be on the cell chromosome. The present study confirmed by using pulsed-field gel electrophoresis and subsequent Southern hybridization that these genes are on a large plasmid. The complete nucleotide sequence of this plasmid was determined by using a combination of inverse PCR and primer walking. The sequence was 106,981 bp long and contained 123 potential open reading frames, including the
    <italic>c2I</italic>
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    <italic>c2II</italic>
    genes. The 57 products of these open reading frames had sequences similar to those of well-known proteins. It was speculated that 9 these 57 gene products were related to DNA replication, 2 were responsible for the two-component regulatory system, and 3 were σ factors. In addition, a total of 20 genes encoding proteins related to diverse processes in purine catabolism were found in two regions. In these regions, there were 9 and 11 genes rarely found in plasmids, indicating that this plasmid plays an important role in purine catabolism, as well as in C2 toxin production.

    DOI： 10.1128/jb.01797-08

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  • Botulinum toxin type a (150 kDa) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction Reviewed

    Y. Kitamura, Y. Matsuka, I. Spigelman, Y. Ishihara, Y. Yamamoto, W. Sonoyama, T. Kuboki, K. Oguma

    Neuroscience   159 ( 4 )   1422 - 1429   2009.4

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    DOI： 10.1016/j.neuroscience.2009.01.066

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  • Immune Reactions Against Elongation Factor 2 Kinase: Specific Pathogenesis of Gastric Ulcer from Helicobacter pylori Infection Reviewed

    Kiyoshi Ayada, Kenji Yokota, Yoshiro Kawahara, Yumiko Yamamoto, Kazuyuki Hirai, Tomoki Inaba, Masahide Kita, Hiroyuki Okada, Kazuhide Yamamoto, Keiji Oguma

    CLINICAL & DEVELOPMENTAL IMMUNOLOGY   2009

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORPORATION  

    Helicobacter pylori (H. pylori) infection is a definite causative factor for gastric ulcers (GUs). In the present study we detected a specific antigen of gastric epithelial cells (HGC-27) using cell ELISA, which was recognized by the sera of GU patients (n = 20) but not in patients with chronic gastritis (CG; n = 20) or in healthy volunteers (HC; n = 10). This antigen was over-expressed by a stressful (heat-stressed) environment, and was identified as elongation factor 2 kinase (EF-2K) by western blotting. The GU patients&apos; lymphocytes stimulated by H. pylori specifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes) from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1) and cytotoxic T lymphocyte (CTL) as opposed to those from CG patients. The target cells (HGC-27) expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU. Copyright (C) 2009 Kiyoshi Ayada et al.

    DOI： 10.1155/2009/850623

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  • Molecular properties of each subcomponent in Clostridium botulinum type B haemagglutinin complex Reviewed

    Hideyuki Arimitsu, Yoshihiko Sakaguchi, Jae-Chul Lee, Sadayuki Ochi, Kentaro Tsukamoto, Yumiko Yamamoto, Shaobo Ma, Takao Tsuji, Keiji Oguma

    Microbial Pathogenesis   45 ( 2 )   142 - 149   2008.8

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    DOI： 10.1016/j.micpath.2008.04.007

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  • Botulinum toxin blocks neurotransmitter release from somata of rat neuropathic trigeminal ganglion neurons Reviewed

    Kitamura Yoichi, Matsuka Yoshizo, Ishihara Yoshihito, Spigelman Igor, Yamamoto Yumiko, Sonoyama Wataru, Kamioka Horoshi, Yamashiro Takashi, Oguma Keiji, Kuboki Takuo

    TOXICON   51   6 - 6   2008.6

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    Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

    DOI： 10.1016/j.toxicon.2008.04.019

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  • Effects of the PsbP knockdown on the photosynthetic electron transfer in Nicotiana tabacum.

    Kunio Ido, Kentaro Ifuku, Seiko Ishihara, Yumiko Yamamoto, Chikahiro Miyake, Fumihiko Sato

    Photosynthesis Energy from the Sun   5   605 - 608   2008

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    Language：English   Publishing type：Research paper (international conference proceedings)  

    DOI： 10.1007/978-1-4020-6709-9_136

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  • Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory destrusor overactivity Reviewed

    Jae-Chul Lee, Teruhiko Yokoyama, Hyun-Jung Hwang, Hideyuki Arimitsu, Yumiko Yamamoto, Makiko Kawasaki, Tomoko Takigawa, Kouichi Takeshi, Atsushi Nishikawa, Hiromi Kumon, Keiji Oguma

    FEMS Immunology & Medical Microbiology   51 ( 1 )   201 - 211   2007.10

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    DOI： 10.1111/j.1574-695x.2007.00301.x

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  • Identification of structural genes for Clostridium botulinum type C neurotoxin-converting phage particles Reviewed

    Hyun-Jung Hwang, Jae-Chul Lee, Yumiko Yamamoto, Mahfuzur R. Sarker, Tomofusa Tsuchiya, Keiji Oguma

    FEMS Microbiology Letters   270 ( 1 )   82 - 89   2007.5

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    DOI： 10.1111/j.1574-6968.2007.00653.x

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  • C Terminal Half Fragment (50 kDa) of Heavy Chain Components of Clostridium botulinum Type C and D Neurotoxins Can Be Used as an Effective Vaccine

    Jae-Chul Lee, Hyun-Jung Hwang, Yoshihiko Sakaguchi, Yumiko Yamamoto, Hideyuki Arimitsu, Takao Tsuji, Toshihiro Watanabe, Tohru Ohyama, Tomofusa Tsuchiya, Keiji Oguma

    Microbiology and Immunology   51 ( 4 )   445 - 455   2007.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1111/j.1348-0421.2007.tb03919.x

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  • Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR)2 and mitogen-activated protein (MAP) kinase pathway in human monocytes Reviewed

    Ying Zhao, Kenji Yokota, Kiyoshi Ayada, Yumiko Yamamoto, Tomayuki Okada, Lianhua Shen, Keiji Oguma

    Journal of Medical Microbiology   56 ( 2 )   154 - 164   2007.2

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    Publishing type：Research paper (scientific journal)   Publisher：Microbiology Society  

    Previous reports have indicated that <italic>Helicobacter pylori</italic> heat-shock protein 60 (<italic>H. pylori</italic>-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by which <italic>H. pylori</italic>-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by which <italic>H. pylori</italic>-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. Intact <italic>H. pylori</italic>, heat-killed <italic>H. pylori</italic> and <italic>H. pylori</italic> recombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 h in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partially inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-<italic>κ</italic>B (NF-<italic>κ</italic>B)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-<italic>κ</italic>B activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway in <italic>H. pylori</italic>-HSP60-induced IL-8 secretion.

    DOI： 10.1099/jmm.0.46882-0

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  • Effect of the PsbP knockdown on the photosynthetic electron transfer in higher plants Reviewed

    Ido Kunio, Ifuku Kentaro, Yamamoto Yumiko, Sato Fumihiko

    PLANT AND CELL PHYSIOLOGY   48   S98   2007

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  • PsbP Protein, But Not PsbQ Protein, Is Essential for the Regulation and Stabilization of Photosystem II in Higher Plants Reviewed

    Kentaro Ifuku, Yumiko Yamamoto, Taka-aki Ono, Seiko Ishihara, Fumihiko Sato

    Plant Physiology   139 ( 3 )   1175 - 1184   2005.11

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    <title>Abstract</title>
    PsbP and PsbQ proteins are extrinsic subunits of photosystem II (PSII) and participate in the normal function of photosynthetic water oxidation. Both proteins exist in a broad range of the oxygenic photosynthetic organisms; however, their physiological roles in vivo have not been well defined in higher plants. In this study, we established and analyzed transgenic tobacco (Nicotiana tabacum) plants in which the levels of PsbP or PsbQ were severely down-regulated by the RNA interference technique. A plant that lacked PsbQ showed no specific phenotype compared to a wild-type plant. This suggests that PsbQ in higher plants is dispensable under the normal growth condition. On the other hand, a plant that lacked PsbP showed prominent phenotypes: drastic retardation of growth, pale-green-colored leaves, and a marked decrease in the quantum yield of PSII evaluated by chlorophyll fluorescence. In PsbP-deficient plant, most PSII core subunits were accumulated in thylakoids, whereas PsbQ, which requires PsbP to bind PSII in vitro, was dramatically decreased. PSII without PsbP was hypersensitive to light and rapidly inactivated when the repair process of the damaged PSII was inhibited by chloramphenicol. Furthermore, thermoluminescence studies showed that the catalytic manganese cluster in PsbP-deficient leaves was markedly unstable and readily disassembled in the dark. The present results demonstrated that PsbP, but not PsbQ, is indispensable for the normal PSII function in higher plants in vivo.

    DOI： 10.1104/pp.105.068643

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  • Post-translational regulation of CND41 protease activity in senescent tobacco leaves

    Yusuke Kato, Yumiko Yamamoto, Shinya Murakami, Fumihiko Sato

    Planta   222 ( 4 )   643 - 651   2005.11

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1007/s00425-005-0011-4

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    Other Link： http://link.springer.com/article/10.1007/s00425-005-0011-4/fulltext.html

  • Structure and function of the PsbP protein of Photosystem II from higher plants Reviewed

    Kentaro Ifuku, Toru Nakatsu, Ren Shimamoto, Yumiko Yamamoto, Seiko Ishihara, Hiroaki Kato, Fumihiko Sato

    Photosynthesis Research   84 ( 1-3 )   251 - 255   2005.6

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1007/s11120-004-7160-3

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    Other Link： http://link.springer.com/article/10.1007/s11120-004-7160-3/fulltext.html

  • Functional analysis of four members of the PsbP family in photosystem II in Nicotiana tabacum using differential RNA interference Reviewed

    S. Ishihara, Y. Yamamoto, K. Ifuku, F. Sato

    Plant and Cell Physiology   46 ( 12 )   1885 - 1893   2005

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  • Functional analysis of the four PsbP members encoded by a multigene family in Nicotiana tabacum.

    Seiko Ishihara, Yumiko Yamamoto, Kentaro Ifuku, Fumihiko Sato

    Photosynthesis fundamental aspects to global perspectives   2005

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    DOI： 10.14841/jspp.2005.0.012.0

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  • The DNA-binding protease, CND41, and the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase in senescent leaves of tobacco Reviewed

    Yusuke Kato, Shinya Murakami, Yumiko Yamamoto, Hiroshi Chatani, Yoshihiko Kondo, Takeshi Nakano, Akiho Yokota, Fumihiko Sato

    Planta   220 ( 1 )   97 - 104   2004.11

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    DOI： 10.1007/s00425-004-1328-0

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  • Specific RNA Interference in psbP Genes Encoded by a Multigene Family in Nicotiana tabacumwith a Short 3′-Untranslated Sequence Reviewed

    Kentaro IFUKU, Yumiko YAMAMOTO, Fumihiko SATO

    Bioscience, Biotechnology, and Biochemistry   67 ( 1 )   107 - 113   2003.1

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    DOI： 10.1271/bbb.67.107

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  • A sequential two-step proteolytic process in the carboxyl-terminal truncation of precursor D1 protein in Synechocystis sp. PCC68031 Reviewed

    Noritoshi Inagaki, Yumiko Yamamoto, Kimiyuki Satoh

    FEBS Letters   509 ( 2 )   197 - 201   2001.12

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    DOI： 10.1016/s0014-5793(01)03180-5

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  • Overexpression and Characterization of Carboxyl-terminal Processing Protease for Precursor D1 Protein Reviewed

    Yumiko Yamamoto, Noritoshi Inagaki, Kimiyuki Satoh

    Journal of Biological Chemistry   276 ( 10 )   7518 - 7525   2001.3

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    DOI： 10.1074/jbc.m008877200

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  • Possible involvement of two-step processing in the C-terminal cleavage of precursor D1 protein in Synechocystis sp. PCC6803.

    Noritoshi Inagaki, Y. Yamamoto, K. Satoh

    PS2001 Proceedings   S5   022   2001

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  • Some aspects of carboxyl-terminal processing of precursor D1 protein in photosystem II.

    Y. Yamamoto, Noritoshi Inagaki, K. Satoh

    PS2001 Proceedings   S5   023   2001

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  • Competitive inhibition analysis of the enzyme-substrate interaction in the carboxy-terminal processing of the precursor D1 protein of photosystem II reaction center using substituted oligopeptides Reviewed

    Yumiko Yamamoto, Kimiyuki Satoh

    FEBS Letters   430 ( 3 )   261 - 265   1998.7

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    DOI： 10.1016/s0014-5793(98)00671-1

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  • Processing of precursor D1 protein in the PSII membrane by CtpA over-expressed in E-coli - An analysis using an antibody which specifically recognizes the cleavage product. Reviewed

    Y Yamamoto, K Satoh

    PHOTOSYNTHESIS: MECHANISMS AND EFFECTS, VOLS I-V   3131 - 3134   1998

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  • Genetic Engineering of the Processing Site of D1 Precursor Protein of Photosystem II Reaction Center in Chlamydomonas reinhardtii

    Y. Takahashi, K. Utsumi, Y. Yamamoto, A. Hatano, K. Satoh

    Plant and Cell Physiology   37 ( 2 )   161 - 168   1996.3

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    The D1 protein (D1) of photosystem II (PSII) reaction center is synthesized as a precursor (pD1) and then processed at its carboxyl terminus to establish the function of water cleavage. The amino acid sequence of the carboxyl terminal extension excised by this process is poorly con-served except for a residue after the cleavage site at position of 345. We have constructed a vector for site-directed mutagenesis of the chloroplast psbA gene encoding D1 of the green alga, Chlamydomonas reinhardtii. The vector enables one to transform the chloroplasts of a psbA deletion mutant (Fud7) and directly select transformants for resistance to spectinomycin. Using this transforming vector, we have substituted Ser345 to Gly, Cys, Val and Phe in order to investigate effects of the amino acid side chain at this position on the processing rate. All of the resulting transformants exhibited the PSII activity as wild type and grew normally under photoautotrophic conditions even under strong light where rapid turnover of D1 protein is expected to occur. Western blotting analysis demonstrated that mature D1 accumulates in these transformants at wild type level. Pulse and chase labeling of chloroplast-encoded proteins using [^<35>S]sulfate revealed that the processing of D1 precursor protein occurs in all four transformants as efficiently as in wild type, at least under the experimental conditions examined. The results suggest that either the amino acid side chain at position of 345 (+1 position) is not crucial to the enzymatic cleavage of pD1 in vivo or the apparent rate of processing in vivo is not limited by the enzymatic cleavage.

    DOI： 10.1093/oxfordjournals.pcp.a028927

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  • Carboxyl-terminal processing protease for the D1 precursor protein: cloning and sequencing of the spinach cDNA

    Noritoshi Inagaki, Yumiko Yamamoto, Hitoshi Mori, Kimiyuki Satoh

    Plant Molecular Biology   30 ( 1 )   39 - 50   1996.1

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    DOI： 10.1007/bf00017801

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  • Recognition of the Structure around the Site of Cleavage by the Carboxyl-terminal Processing Protease for D1 Precursor Protein of the Photosystem II Reaction Center Reviewed

    Fumiko Taguchi, Yumiko Yamamoto, Kimiyuki Satoh

    Journal of Biological Chemistry   270 ( 18 )   10711 - 10716   1995.5

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    DOI： 10.1074/jbc.270.18.10711

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  • Recognition signal for the C-terminal processing protease of D1 precursor protein in the photosystem II reaction center. An analysis using synthetic oligopeptides Reviewed

    Fumiko Taguchi, Yumiko Yamamoto, Noritoshi Inagaki, Kimiyuki Satoh

    FEBS Letters   326 ( 1-3 )   227 - 231   1993.7

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    DOI： 10.1016/0014-5793(93)81796-3

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MISC

  • Implications for bacterial evolution of giant phages with uracil-containing DNA genomes

    内山淳平, 内山伊代, 後藤和義, 山本由弥子, 松崎茂展, 松下治

    日本細菌学雑誌(Web)   78 ( 1 )   2023

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  • 敗血症性肺塞栓症患者から分離されたTsukamurella inchonensisの同定(Identification of Tsukamurella inchonensis isolated from septic pulmonary emboli(SPE) patient)

    I Putu Bayu Mayura, Gotoh Kazuyoshi, 美間 健彦, 山本 由弥子, 横田 憲治, 松下 治, 萩谷 英大

    日本細菌学雑誌   76 ( 1 )   89 - 89   2021.2

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  • 細菌性コラゲナーゼのコラーゲン・アンカーの構造活性相関と歯周病治療への応用

    松下 治, 美間 健彦, 後藤 和義, 山本 由弥子, Caviness Perry, Sakon Joshua, 内田 健太郎, 中村 心, 岡本 健太郎, 高柴 正悟

    日本細菌学雑誌   75 ( 1 )   138 - 138   2020.1

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  • 細菌性コラゲナーゼのコラーゲン・アンカーと歯周組織再生への応用(Collagen anchors of bacterial collagenases and their application to periodontal tissue regeneration)

    松下 治, 美間 健彦, 後藤 和義, 山本 由弥子, Perry Caviness, Sakon Joshua, 小出 隆規, 内田 健太郎, 中村 心, 高柴 正悟

    日本細菌学雑誌   74 ( 1 )   84 - 84   2019.3

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  • C型とD型ボツリヌス毒素変換ファージの解析(Analysis of botulinum neurotoxin-converting phages in Clostridium botulinum types C and D)

    阪口 義彦, 内山 淳平, 小椋 義俊, 後藤 和義, 山本 由弥子, 松崎 茂展, 山口 明日美, 林 哲也, 小熊 惠二, 林 俊治

    日本細菌学雑誌   73 ( 1 )   94 - 94   2018.2

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  • 細菌性コラゲナーゼのPKDドメインの構造機能解析と骨新生誘導剤の開発(Structure analysis of bacterial collagenases to develop therapeutics to induce osteogenesis)

    松下 治, 内田 健太郎, 美間 健彦, 後藤 和義, 山本 由弥子, 横田 憲治, Bauer Ryan, 高相 晶士, Sakon Joshua

    日本細菌学雑誌   73 ( 1 )   114 - 114   2018.2

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  • C型とD型ボツリヌス毒素変換ファージの解析(Analysis of botulinum neurotoxin-converting phages in Clostridium botulinum types C and D)

    阪口 義彦, 内山 淳平, 小椋 義俊, 後藤 和義, 山本 由弥子, 松崎 茂展, 山口 明日美, 林 哲也, 小熊 惠二, 林 俊治

    日本細菌学雑誌   73 ( 1 )   94 - 94   2018.2

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  • 細菌性コラゲナーゼのマトリックス・アンカーの構造解析と骨新生誘導のための複合剤開発(Structural analysis of a matrix anchor in bacterial collagenase to develop an osteogenic therapeutic)

    松下 治, 内田 健太郎, 関口 裕之, 美間 健彦, 後藤 和義, 山本 由弥子, 横田 憲治, 高相 晶士, Bauer Ryan, Sakon Joshua

    日本細菌学雑誌   72 ( 1 )   109 - 109   2017.2

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  • Vibrio alginolyticusのコラゲナーゼ発現はHapRにより調節される(Expression of colA is regulated by HapR in Vibrio alginolyticus)

    美間 健彦, 西川 裕太郎, 中田 悠介, 波多野 直哉, 後藤 和義, 山本 由弥子, 横田 憲治, 松下 治

    日本細菌学雑誌   72 ( 1 )   106 - 106   2017.2

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  • C型ボツリヌス毒素変換ファージのゲノム比較と遺伝子機能解析(The genome sequence of Clostridium botulinum type C phage and functional analysis of gene products)

    阪口 義彦, 内山 淳平, 小椋 義俊, 山本 由弥子, 松崎 茂展, 林 哲也, 松下 治, 小熊 惠二, 林 俊治

    日本細菌学雑誌   71 ( 1 )   135 - 135   2016.2

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  • 合成コラーゲン様基剤とコラーゲン結合型線維芽細胞増殖因子を用いた複合剤による骨形成促進法の開発

    濱本 奈々, 内田 健太郎, 関口 裕之, 美間 健彦, 後藤 和義, 山本 由弥子, 横田 憲治, 高相 晶士, 松下 治

    日本細菌学雑誌   71 ( 1 )   126 - 126   2016.2

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  • Vibrio alginolyticus I.029のコラゲナーゼ発現はHapRにより調節される

    西川 裕太郎, 美間 健彦, 中田 悠介, 後藤 和義, 山本 由弥子, 横田 憲治, 松下 治

    日本細菌学雑誌   71 ( 1 )   127 - 127   2016.2

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  • Clostridium argentinenseにおけるG型ボツリヌス神経毒素遺伝子をコードするプラスミドの分析(Analysis of botulinum neurotoxin type G gene-encoding plasmid in Clostridium argentinense)

    阪口 義彦, 内山 淳平, 鈴木 智典, 山本 由弥子, 小椋 義俊, 細見 晃司, 松崎 茂展, 林 哲也, 小崎 俊司, 小熊 惠二

    日本細菌学雑誌   69 ( 1 )   236 - 236   2014.2

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  • C型ボツリヌス毒素変換ファージのコアゲノムの探索

    阪口義彦, 内山淳平, 小椋義俊, 山本由弥子, 鈴木智典, 松崎茂展, 林哲也, 小熊惠二

    日本細菌学雑誌   68 ( 1 )   178 - 178   2013.2

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  • 神経障害性疼痛へのボツリヌス毒素の効果

    松香芳三, 丸濵功太郎, 三宅愛, 山本由弥子, 前川賢治, 古味佳子, 園山亘, 小熊惠二, 窪木拓男

    歯界展望   65 ( 5 )   666 - 666   2013

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  • BOTULINUM TOXIN TYPE A (150 kDa) DECREASES EXAGGERATED NEUROTRANSMITTER RELEASE FROM TRIGEMINAL GANGLION NEURONS AND RELIEVES NEUROPATHY BEHAVIORS INDUCED BY INFRAORBITAL NERVE CONSTRICTION (vol 159, pg 1422, 2009)

    Y. Kitamura, Y. Matsuka, I. Spigelman, Y. Ishihara, Y. Yamamoto, W. Sonoyama, H. Kamioka, T. Yamashiro, T. Kuboki, K. Oguma

    NEUROSCIENCE   161 ( 3 )   950 - 950   2009.7

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    DOI： 10.1016/j.neuroscience.2009.04.067

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  • 三叉神経痛治療のための薬物治療法の開発

    松香芳三, 北村洋一, 山本由弥子, 園山 亘, Spigelman I, 小熊恵二, 窪木拓男

    日本歯科医学会誌   28 ( 1 )   49 - 53   2009

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    高齢者に多発する三叉神経痛の病態解明は現時点では十分とは言えず、根本的な治癒が得られずに激痛に苛まれている患者も少なくない。治療には抗てんかん薬や抗うつ薬などが用いられるが、それらの薬物が有するめまいやふらつきなどの中枢性副作用のため継続服用が不可能となることがある。我々は三叉神経痛などの慢性難治性疼痛に対する中枢性副作用の少ない治療法開発のため、研究を継続している。現在、毒素成分のみを精製した改良型ボツリヌス毒素(BoNT)を投与することにより、三叉神経節細胞における神経伝達物質の遊離が抑制されるのか、BoNTの末梢への注射により、三叉神経痛モデル動物の疼痛を抑制することができるのかを検討している。三叉神経痛モデルラットでは、三叉神経節細胞において神経伝達物質の遊離が増加していた。また、三叉神経痛モデルラットでは、疼痛閾値が低下しており、このラットモデルが疼痛を有していることが理解できた。このモデルラットの顔面部皮膚にBoNTを注射することにより、疼痛閾値が上昇し、疼痛が減弱することが確認できた。以上より、三叉神経痛患者治療において中枢性副作用を誘発しない、新しい治療法の開発に新たな展開が見られた。(著者抄録)

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  • 三叉神経因性疼痛モデルラットにおける改良A型ボツリヌス毒素の効果

    北村 洋一, 松香 芳三, 石原 嘉人, 園山 亘, 山本 由弥子, 小熊 恵二, 窪木 拓男

    日本口腔顔面痛学会雑誌   1 ( 1 )   69 - 69   2008.12

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  • Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory detrusor overactivity

    Keiji Oguma, Jae-Chul Lee, Teruyuki Yokoyama, Yumiko Yamamoto, Yoshihiko Sakaguchi, Shaobo Ma, Hideyuki Arimitsu

    TOXICON   51   41 - 41   2008.6

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    DOI： 10.1016/j.toxicon.2008.04.122

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  • The effect of peripheral administration of botulinum toxin type A in rats with neuropathic pain

    Yoshizo Matsuka, Yoichi Kitamura, Igor Spigelman, Rahena Akther, Yumiko Yamamoto, Wataru Sonoyama, Keiji Oguma, Takuo Kuboki

    TOXICON   51   7 - 7   2008.6

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    DOI： 10.1016/j.toxicon.2008.04.020

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  • Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory destrusor overactivity (vol 51, pg 201, 2007)

    Jae-Chul Lee, Teruhiko Yokoyama, Hyun-Jung Hwang, Hideyuki Arimitsu, Yumiko Yamamoto, Makiko Kawasaki, Tomoko Takigawa, Kouichi Takeshi, Atsushi Nishikawa, Hiromi Kumon, Keiji Oguma

    FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY   51 ( 3 )   587 - 587   2007.12

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    DOI： 10.1111/j.1574-695X.2007.00351.x

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  • Effects of the PsbP knockdown on the photosynthetic electron transfer in Nicotiana tabacum.

    K. Ido, K. Ifuku, S. Ishihara, Y. Yamamoto, C. Miyake, F. Sato

    PHOTOSYNTHESIS RESEARCH   91 ( 2-3 )   192 - 192   2007.2

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  • Structures and functional differentiation of the extrinsic subunits of photosystem II

    K Ifuku, Y Yamamoto, F Sato

    PLANT AND CELL PHYSIOLOGY   47   S9 - S9   2006

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  • Down-regulation of psbO, psbP and psbQ genes in Nicotiana tabacum by RNA interference technique

    K Ifuku, Y Yamamoto, S Ishihara, F Sato

    PLANT AND CELL PHYSIOLOGY   46   S27 - S27   2005

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  • Functional analysis of the psbP gene family in Nicotiana tabacum

    S Ishihara, Y Yamamoto, K Ifuku, F Sato

    PLANT AND CELL PHYSIOLOGY   45   S80 - S80   2004

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  • Suppression of psbP genes in Nicotiana tabacum by RNAi

    Y Yamamoto, K Ifuku, S Ishihara, F Sato

    PLANT AND CELL PHYSIOLOGY   45   S221 - S221   2004

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  • Processing of CND41 might be important for the activation of protease activity

    Y Kato, Y Yamamoto, F Sato

    PLANT AND CELL PHYSIOLOGY   45   S59 - S59   2004

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  • CARBOXYL-TERMINAL EXTENSION OF PRECURSOR D1 PROTEIN IS EXCISED WITH TWO STEPS BY CTPA IN SYNECHOCYSTIS 6803 :

    INAGAKI Noritoshi, YAMAMOTO Yumiko, SATOH Kimiyuki

    Plant and cell physiology   42   s171   2001

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  • セネデスムスLF-1株を用いたD1タンパク質C-末プロセシングの解析

    山本 由弥子, 稲垣 言要, 佐藤 公行

    日本植物学会大会研究発表記録 = Proceedings of the annual meeting of the Botanical Society of Japan   61   194 - 194   1997.9

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  • 光化学系II反応中心D1タンパク質のC末端切断酵素の部位特異的突然変異による触媒中心の解析

    稲垣 言要, PAKRASI Himadri, 山本 由弥子, 佐藤 公行

    日本植物学会大会研究発表記録 = Proceedings of the annual meeting of the Botanical Society of Japan   61   206 - 206   1997.9

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  • ホウレンソウD1タンパク質前駆体C-末切断酵素の大腸菌における発現

    山本 由弥子, 松本 哲, 稲垣 言要, 佐藤 公行

    日本植物学会大会研究発表記録 = Proceedings of the annual meeting of the Botanical Society of Japan   60   214 - 214   1996.10

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Research Projects

  • Preclinical study on botulinum toxin therapy in treatment for neuropathic pain

    Grant number：17K01358  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YAMAMOTO Yumiko

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    We have previously shown that botulinum toxin type A (BoNT/A) alleviates trigeminal neuropathy induced by infraorbital nerve constriction. In this study, we generated two rat models of chemotherapy-induced peripheral neuropathy, and assessed the analgesic effect of BoNT/A in chemotherapy-induced neuropathy. Unilateral BoNT/A administration into the whisker pad area attenuated chemotherapy-induced mechanical allodynia bilaterally.
    In addition, we investigated the cleavage of synaptobrevin and syntaxin in the trigeminal ganglion neurons by botulinum toxin type B (BoNT/B) and by botulinum toxin type C (BoNT/C) respectively, to apply BoNT/B and BoNT/C to treatment for neuropathic pain.

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  • Neural transmission mechanisms of tooth mechanical stimulation -Development of treatment for occlusal dysesthesia patients-

    Grant number：26293412  2014.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    MATSUKA Yoshizo

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    Grant amount：\16120000 （ Direct expense: \12400000 、 Indirect expense：\3720000 ）

    Rat premolar teeth were mechanically stimulated and the active part of the brain was measured by PET using FDG. Rats under anesthesia stimulated the right maxillary permolar while measuring the stimulation strength using an electric von Frei device. Before the stimulation of the teeth, FDG was injected from a tail vein and stimulated with a strength of 100, 200, 300 g. The brain PET image was divided into 4 parts (upper right, upper left, lower right, lower left) and the peak value of FDG accumulation was measured. As a result, the stimulation at 300 g showed more FDG accumulation than the 100 or 200 g stimulation. In addition, there were more FDG accumulation was observed in the trigeminal ganglion and the sensory part when the brain was classified into the sensory area, the motor area, hippocampus, trigeminal ganglion and spinal cord.

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  • Clarification of molecular mechanisms underlying the analgesic effect of botulinum toxin and applied study

    Grant number：26350499  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YAMAMOTO YUMIKO, MATSUSHITA Osamu, OGUMA Keiji

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    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    We developed an assay to measure the proteolytic activity of botulinum toxin (BoNT), and attempted to synthesize fluorescently labeled full-length BoNT, in order to study molecular mechanisms for the analgesic effect of BoNT. We also generated four kinds of anti-peptide antibodies against SNAP-25, and showed that BoNT/A or BoNT/E cleaves SNAP-25 in cultured trigeminal ganglion neurons. This suggests that peripherally administered BoNT decreases the release of neurotransmitters via the proteolysis of SNARE proteins in sensory ganglion neurons and relieves neuropathic pain.

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  • Development of neuro-regeneration with Botulinum toxin

    Grant number：23659897  2011 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    MATSUKA Yoshizo, KUBOKI Takuo, MATSUO Ryuji, OGUMA Keiji, YAMAMOTO Yumiko, KUMADA Ai

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    Grant amount：\3510000 （ Direct expense: \2700000 、 Indirect expense：\810000 ）

    Dissociated rat trigeminal ganglion somata were incubated with matrigel in 37℃ CO_2condition. Commercially available hippocampus neuron was used in this study. Neuronal change was observed and the neuron that incubated with type A Botulinum toxin was survived longer than control. Also, dendrite of the neuron with Rotulinum toxin was longer than control neuron.

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  • Development of a new treatment for trigeminal neuron sensitization

    Grant number：22390365  2010.04 - 2014.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    MATSUKA Yoshizo, KUBOKI Takuo, YAMAMOTO Yumiko, KUMADA Ai, OGUMA Keiji

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    Grant amount：\18720000 （ Direct expense: \14400000 、 Indirect expense：\4320000 ）

    Fluorescein labeled botulinum toxin heavy chain which works for endocytosis was injected into rat face skin and found in ipsilateral trigeminal ganglion. The labeled botulinum toxin heavy chain was not found on the contralateral side or in the only fluorescein injection. The uptake was inhibited by colchicine treatment, which blocks axonal transport. Intradermal injection of botulinum toxin alleviates infraorbital nerve constriction induced thermal hyperalgesia in an operant assay. Direct application of botulinum toxin to dorsal root ganglia reversed the sciatic nerve entrapment induced decreases in withdrawal thresholds.

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  • The development of novel drug delivery systems based on the mechanism for intestinal absorption of botulinum toxins

    Grant number：22500427  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YAMAMOTO Yumiko, OGUMA Keiji

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    In food-borne botulism, the orally ingested botulinum neurotoxins, which could be classified into seven types (A to G) based on their antigenicity, must be absorbed from the small intestine. In this study, we produced the liposomes modified with HA, which is a non-toxic component of the type A botulinum toxin complex, in order to develop novel intestine-targeted drug delivery systems. On the other hand, we showed that the type E botulinum toxin might bind to the intestinal cells via the Hc domain of neurotoxin.

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  • Establishment of new procedure for botulism including bioterrorism, and application of botulinum toxin to the treatment

    Grant number：19390126  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    OGUMA Keiji, YOKOTA Kenji, AYADA Kiyoshi, SAKAGUCHI Yoshihiko, YAMAMOTO Yumiko, ARIMITSU Hideyuki

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    Grant amount：\19110000 （ Direct expense: \14700000 、 Indirect expense：\4410000 ）

    ボツリヌス菌や毒素、抗毒素抗体の検出方法と毒素の治療への応用を検討した。菌の検出法としては、A~F型毒素遺伝子を増幅できるPCRを開発した。毒素の検出法としてはイムノクロマト法を開発したが、現在、改良中である。抗体の検出法としては、毒素の一部を結合させたカラムを用いて抗体を濃縮して検出する方法を開発した。治療への応用としては、三叉神経痛と前立腺肥大症に適用できることをとラットを用いて実証した。

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  • Basic mechanisms of nociceptive sensitization of first order sensory neuron in trigeminal neuralgia and treatment development

    Grant number：18390512  2006 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    MATSUKA Yoshizo, MAEKAWA Kenji, KUBOKI Takuo, KANYAMA Manabu, SUGIMOTO Tomosada, TAKEI Koji, ONO Tsuyoshi, OGUMA Keiji, YAMAMOTO Yomiko, KITAMURA Yoichi, KUMADA Ai, SPIGELMAN Igor, NEUBERT John k.

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    Grant amount：\16850000 （ Direct expense: \14300000 、 Indirect expense：\2550000 ）

    We found that trigeminal nerve constriction induced facial pain and increased neurotransmitter release from trigeminal ganglion cell body. Also, facial injection of highly purified Botulinum toxin type A 150 kDa (BoNT/A/A) decreased the pain level and the neurotransmitter release.
    These results made clear the mechanisms of trigeminal neuralgia and peripheral BoNT/A injection may be an important treatment in the near future.

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