2025/03/27 更新

写真a

アオト　マモル
青戸　守
Aoto Mamoru
所属
大学院医学系研究科 医学専攻 准教授
職名
准教授
連絡先
メールアドレス
ホームページ
https://www.m.ehime-u.ac.jp/school/physiology2/
外部リンク

学位

  • 理学博士 （ 神戸大学 ）

研究分野

  • ライフサイエンス / 生理学  / RNAバイオロジー

  • ライフサイエンス / 医療薬学  / RNAバイオロジー

所属学協会

委員歴

  • 松山市   土壌汚染対策専門委員  

    2009年11月 - 現在   

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    団体区分：自治体

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論文

  • Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior. 査読

    Ohkubo N, Aoto M, Kon K, Mitsuda N

    Life Science   2019年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

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  • Transferrin receptor 1 is required for enucleation of mouse erythroblasts during terminal differentiation 査読

    Mamoru Aoto, Akiho Iwashita, Kanako Mita, Nobutaka Ohkubo, Yoshihide Tsujimoto, Noriaki Mitsuda

    FEBS Open Bio   9 ( 2 )   291 - 303   2019年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

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  • Zinc fnger protein 521 involved in small intestinal function and stem cell differentiation 査読

    Nazuna Morisada, Kotone Miyake, Mamoru Aoto, Noriaki Mitsuda, Nobutaka Ohkubo

    JOURNAL OF PHYSIOLOGICAL SCIENCES   69   S163   2019年

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  • Abnormal Behaviors and Developmental Disorder of Hippocampus in Zinc Finger Protein 521 (ZFP521) Mutant Mice 査読

    Nobutaka Ohkubo, Etsuko Matsubara, Jun Yamanouchi, Rie Akazawa, Mamoru Aoto, Yoji Suzuki, Ikuya Sakai, Takaya Abe, Hiroshi Kiyonari, Seiji Matsuda, Masaki Yasukawa, Noriaki Mitsuda

    PLOS ONE   9 ( 3 )   e92848   2014年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

    Zinc finger protein 521 (ZFP521) regulates a number of cellular processes in a wide range of tissues, such as osteoblast formation and adipose commitment and differentiation. In the field of neurobiology, it is reported to be an essential factor for transition of epiblast stem cells into neural progenitors in vitro. However, the role of ZFP521 in the brain in vivo still remains elusive. To elucidate the role of ZFP521 in the mouse brain, we generated mice lacking exon 4 of the ZFP521 gene. The birth ratio of our ZFP521(Delta/Delta) mice was consistent with Mendel's laws. Although ZFP521(Delta/Delta) pups had no apparent defect in the body and were indistinguishable from ZFP521(+/+) and ZFP521(+/Delta) littermates at the time of birth, ZFP521(Delta/Delta) mice displayed significant weight reduction as they grew, and most of them died before 10 weeks of age. They displayed abnormal behavior, such as hyper-locomotion, lower anxiety and impaired learning, which correspond to the symptoms of schizophrenia. The border of the granular cell layer of the dentate gyrus in the hippocampus of the mice was indistinct and granular neurons were reduced in number. Furthermore, Sox1-positive neural progenitor cells in the dentate gyrus and cerebellum were significantly reduced in number. Taken together, these findings indicate that ZFP521 directly or indirectly affects the formation of the neuronal cell layers of the dentate gyrus in the hippocampus, and thus ZFP521(Delta/Delta) mice displayed schizophrenia-relevant symptoms. ZFP521(Delta/Delta) mice may be a useful research tool as an animal model of schizophrenia.

    DOI： 10.1371/journal.pone.0092848

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  • Accelerated destruction of erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice 査読

    Nobutaka Ohkubo, Yoji Suzuki, Mamoru Aoto, Jun Yamanouchi, Satoshi Hirakawa, Masaki Yasukawa, Noriaki Mitsuda

    LIFE SCIENCES   93 ( 9-11 )   380 - 387   2013年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

    Aims: STAT3 is a key modulator of activation and differentiation of macrophages. But it is still unknown if deficiency of STAT3 activates macrophages to destroy erythrocytes by phagocytosis. We generated STAT3 conditional knockout mice by crossing foxed STAT3 mice with Tie2 promoter-driven Cre-recombinase transgenic mice and clarified that Stat3 plays a critical role in the formation and activation of macrophages.
    Main methods: Blood cell count, reticulocyte count, serum lactate dehydrogenase, erythropoietin, iron and ferritin concentration, and life span of the erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice were analyzed. To explore the erythropoietic function of the mice, we subjected them to brief hemolytic anemia by injecting them intraperitoneally with phenylhydrazine. The fragility of erythrocytes was examined by scanning electron microscopy and osmotic tolerance test.
    Key findings: The conditional knockout mice had mild normocytic anemia. They also displayed higher lactate dehydrogenase, ferritin and erythropoietin concentration, higher reticulocyte count, and a shorter lifespan of erythrocytes compared with wild-type controls. These data suggest that destruction of erythrocytes and secondary blood formation were accelerated in the STAT3 conditional knockout mice. It didn't appear due to the fragility of erythrocytes. A few of the conditional knockout mice suddenly developed acute severe anemia, high body temperature and massive splenomegaly, and died within 2 weeks after the onset of anemia.
    Significance: This study provided evidence that STAT3 have a critical role in the destruction of erythrocytes by resident macrophages in the spleen. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

    DOI： 10.1016/j.lfs.2013.07.025

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  • Histochemical analysis of brain from neural differentiation factor Zfp521 deficient mice 査読

    Akazawa Rie, Ohkubo Nobutaka, Aoto Mamoru, Suzuki Yoji, Matsubara Etsuko, Yamanouchi Jun, Sakai Ikuya, Yasukawa Masaki, Mitsuda Noriaki

    JOURNAL OF PHYSIOLOGICAL SCIENCES   63   S126   2013年

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  • Study of a mechanism of protective effect with saponins from Panax Ginseng against oxidative stress in blood preservation 査読

    Kono Yusuke, Izumi Ryo, Kono Hiroki, Suzuki Yoji, Ohkubo Nobutaka, Samukawa Keiichi, Aoto Mamoru, Mitsuda Noriaki

    JOURNAL OF PHYSIOLOGICAL SCIENCES   63   S173   2013年

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  • Preventive effect of lignan on redox status of erythrocyte membrane against oxidative stress 査読

    Sato Masatoshi, Okada Nanae, Suzuki Yoji, Ohkubo Nobutaka, Aoto Mamoru, Yamauchi Satoshi, Mitsuda Noriaki

    JOURNAL OF PHYSIOLOGICAL SCIENCES   63   S230   2013年

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  • Transferrin-Transferrin receptor 1 signaling is required for mouse erythroblast enucleation through the mechanism independent of iron uptake 査読

    Onji Hiroshi, Kono Ryoma, Suzuki Yoji, Ohkubo Nobutaka, Mitsuda Noriaki, Tsujimoto Yoshihide, Aoto Mamoru

    JOURNAL OF PHYSIOLOGICAL SCIENCES   63   S173   2013年

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  • Essential role of p38 MAPK in caspase-independent, iPLA(2)-dependent cell death under hypoxia/low glucose conditions 査読

    Mamoru Aoto, Koei Shinzawa, Yoji Suzuki, Nobutaka Ohkubo, Noriaki Mitsuda, Yoshihide Tsujimoto

    FEBS LETTERS   583 ( 10 )   1611 - 1618   2009年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

    The mechanisms of cell death induced by hypoxia or ischemia are not yet fully understood. We have previously demonstrated that cell death induced by hypoxia occurs independently of caspases, and is mediated by phospholipase A(2) (PLA(2)).
    Here, we show that p38 mitogen-activated protein kinase is activated under hypoxia. A selective inhibitor of p38 or decrease in the p38alpha protein level prevents hypoxia-induced cell death. The p38 inhibitor abolishes PLA(2) activation by hypoxia, indicating that p38 acts upstream of PLA(2). The antioxidant N-acetyl-cysteine inhibits activation of p38 and cell death induced by hypoxia, indicating that reactive oxygen species (ROS) are responsible for p38 activation. These results demonstrate that the ROS/p38/PLA(2) signaling axis has a crucial role in caspase-independent cell death induced by hypoxia. Crown Copyright (C) 2009 Published by Elsevier B. V. on behalf of Federation of European Biochemical society. All rights reserved.

    DOI： 10.1016/j.febslet.2009.04.028

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  • EFFECT OF GINSENOSIDES ON RHEOLOGICAL FUNCTIONS OF ERYTHROCYTES AGAINST OXIDATIVE STRESS 査読

    Yoji Suzuki, Nobutaka Ohkubo, Keiichi Samukawa, Mamoru Aoto, Masahiro Sakanaka, Noriaki Mitsuda

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   500 - 500   2009年

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    記述言語：英語   出版者・発行元：SPRINGER TOKYO  

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  • ESSENTIAL ROLE OF P38 MAPK IN CASPASE-INDEPENDENT, PHOSPHOLIPASE A2-DEPENDENT CELL DEATH UNDER HYPOXIA/LOW GLUCOSE CONDITIONS 査読

    Mamoru Aoto, Koei Shinzawa, Yoji Suzuki, Nobutaka Ohkubo, Noriaki Mitsuda, Yoshihide Tsujimoto

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   159 - 159   2009年

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    記述言語：英語   出版者・発行元：SPRINGER TOKYO  

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  • Protective effect of ginsenosides Rg(2) and Rh-1 on oxidation-induced impairment of erythrocyte membrane properties 査読

    Keiichi Samukawa, Yoji Suzuki, Nobutaka Ohkubo, Mamoru Aoto, Masahiro Sakanaka, Noriaki Mitsuda

    BIORHEOLOGY   45 ( 6 )   689 - 700   2008年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IOS PRESS  

    The extract from Panax ginseng has been reported to improve the microcirculation in various organs. However, the mechanisms underlying this phenomenon are still poorly understood. In the present study, using the rheological properties of erythrocytes as an index, we have screened the components of Panax ginseng extract and identified Rg(2) and Rh-1 as the active ingredients. These two ginsenosides prevented the oxidative stress-induced elevation of erythrocyte suspension viscosity and the impairment of erythrocyte elongation in response to shear stress. Rg2 and Rh1 ginsenosides did not have antioxidant activity in an aqueous phase and did not inhibit the peroxidation of membrane lipids, either. However, they inhibited the oxidation-induced decrease of SH-groups in band 3 (anion exchanger-1), one of the important structural proteins of the erythrocyte membrane, but not in other structural proteins: bands 1 and 2 (spectrins), band 4.2 or band 5 (actin). These results suggest that ginsenosides Rg2 and Rh1 protect the rheological functions of erythrocytes against oxidative stress by preventing the oxidation of SH-groups in band 3 protein.

    DOI： 10.3233/BIR-2008-0516

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  • Participation of caspase-3-like protease in oxidation-induced impairment of erythrocyte membrane properties 査読

    Yoji Suzuki, Nobutaka Ohkubo, Mamoru Aoto, Nobuji Maeda, Iwona Cicha, Tetsuro Miki, Noriaki Mitsuda

    BIORHEOLOGY   44 ( 3 )   179 - 190   2007年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IOS PRESS  

    Erythrocytes are very susceptible to oxidative stress, having a high content of intracellular oxygen and hemoglobin. In the present study, exposure to oxidative stress resulted in a significant impairment of erythrocyte membrane functions, such as deformability and anion exchange. Band 3 protein, also known as anion exchanger-1, plays an important role in these two functions. We show that oxidative stress activated caspase-3 inside the erythrocytes, which resulted in band 3 protein cleavage. Interestingly, inhibition of the caspase-3 with its specific inhibitor not only suppressed the digestion of band 3 protein, but also blunted the functional damage to erythrocytes, such as deformability and anion exchange, without changing the level of peroxidation of membrane lipids. These results provide experimental evidence that activation of caspase-3 plays an important role in the oxidative stress-induced impairment of membrane functions of erythrocytes.

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  • A novel alternative splice variant of nicastrin and its implication in Alzheimer disease 査読

    N Mitsuda, HD Yamagata, WT Zhong, M Aoto, H Akatsu, N Uekawa, K Kamino, K Taguchi, T Yamamoto, M Maruyama, K Kosaka, M Takeda, Kondo, I, T Miki

    LIFE SCIENCES   78 ( 21 )   2444 - 2448   2006年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

    Nicastrin interacts with gamma-secretase complex components predominantly via the N-terminal third of the transmembrane domain. The authentic transmembrane domain is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex. In this study, we have identified a novel alternatively spliced transcript of nicastrun in human brain tissue. This transcript (NCSTN-Delta E16) lacks exon 16 of nicastrin mRNA, which leads to deletion of 71 amino acids just upstream of its transmembrane domain. Its expression pattern was analyzed in the hippocampus of patients with pathologically diagnosed Alzheimer disease (cases) and non-Alzheimer dementia (controls). In patients with the APOE-epsilon 4 allele, the frequency of Alzheimer disease appeared to be increased in the NCSTN-Delta E16-positive group, but the association was not statistically significant. In conclusion, the expression of NCSTN-Delta E16 transcript may confer some additional risk for developing Alzheimer disease beyond the risk due to ApoE-epsilon 4 allele. Further investigation in larger scale population would be necessary to address its potential implication in Alzheimer disease. (c) 2005 Elsevier Inc All rights reserved.

    DOI： 10.1016/j.lfs.2005.10.007

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  • Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation 査読

    S Sahara, M Aoto, Y Eguchi, N Imamoto, Y Yoneda, Y Tsujimoto

    NATURE   401 ( 6749 )   168 - 173   1999年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MACMILLAN MAGAZINES LTD  

    Apoptosis is defined by several unique morphological nuclear changes, such as chromatin condensation and nuclear fragmentation(1). These changes are triggered by the activation of a family of cysteine proteases called caspases(2,3), and caspase-activated DNase (CAD/DPP40)(4,5) and Iamin protease (caspase-6)(6,7) have been implicated in some of these changes. CAD/DFF40 induces chromatin condensation in purified nuclei, but distinct caspase-activated factor(s) may be responsible for chromatin condensations. Here we use an in vitro system to identify a new nuclear factor, designated Acinus, which induces apoptotic chromatin condensation after cleavage by caspase-3 without inducing DNA fragmentation. Immunodepletion experiments showed that Acinus is essential for apoptotic chromatin condensation in vitro, and an antisense study revealed that Acinus is also important in the induction of apoptotic chromatin condensation in cells.

    DOI： 10.1038/43678

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  • A 58-kDa Shc protein is present in Xenopus eggs and is phosphorylated on tyrosine residues upon egg activation 査読

    M Aoto, K Sato, S Takeba, Y Horiuchi, T Iwasaki, AA Tokmakov, Y Fukami

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   258 ( 2 )   265 - 270   1999年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC  

    A 58-kDa protein was detected in Xenopus egg lysate by SDS-PAGE and immunoblotting with an antibody raised against adaptor protein Shc, a well known tyrosine kinase substrate in numerous biological events. Tyrosine phosphorylation of the Xenopus Shc protein (p58 xShc) was found to increase 2.3 +/- 0.4-fold (n = 3) upon fertilization. Pretreatment of eggs with the tyrosine kinase inhibitor genistein effectively blocked the fertilization-dependent phosphorylation. Tyrosine phosphorylation of p58 xShc was also observed when eggs were activated parthenogenetically by an integrin-interacting RODS-peptide which is known to cause egg activation accompanied by intracellular calcium release. On the other hand, other egg-activating treatments such as electrical shock and calcium ionophore, which directly induce the elevation of intracellular calcium, did not show such an effect. It is also suggested that the phosphorylated p58 xShc may play a role unique to the egg activation process because we found that there was no increase of Shc-Grb2 complex after fertilization. These results demonstrate that p58 xShc is a substrate of egg tyrosine kinases which may be activated by sperm-egg interaction and suggest that the phosphorylated p58 xShc may act upstream of the calcium-dependent pathway of egg activation. (C) 1999 Academic Press.

    DOI： 10.1006/bbrc.1999.0624

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  • Involvement of protein-tyrosine phosphorylation and dephosphorylation in sperm-induced Xenopus egg activation 査読

    K Sato, T Iwasaki, Tamaki, I, M Aoto, AA Tokmakov, Y Fukami

    FEBS LETTERS   424 ( 1-2 )   113 - 118   1998年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

    We have analyzed tyrosine-phosphorylated proteins in Xenopus laevis eggs before and after fertilization by immunoblotting with anti-phosphotyrosine antibody. A number of egg proteins with different subcellular distribution became tyrosine-phosphorylated or dephosphorylated within 30 min after insemination. Tyrosine kinase-specific inhibitors genistein and herbimycin A were found to inhibit sperm-induced egg activation judged by the egg cortical contraction. Surprisingly, sodium orthovanadate, a tyrosine phosphatase inhibitor, also inhibited the egg activation. Moreover, we found that fertilization-dependent tyrosine dephosphorylation of 42-kDa mitogen-activated protein kinase was inhibited in genistein-treated eggs. These results suggest that both protein-tyrosine phosphorylation and dephosphorylation pathways play an important role in the sperm-induced Xenopus egg activation. (C) 1998 Federation of European Biochemical.

    DOI： 10.1016/S0014-5793(98)00123-9

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  • Tyrosine residues 239 and 240 of Shc are phosphatidylinositol 4,5-bisphosphate-dependent phosphorylation sites by c-Src 査読

    K Sato, N Gotoh, T Otsuki, M Kakumoto, M Aoto, AA Tokmakov, M Shibuya, Y Fukami

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   240 ( 2 )   399 - 404   1997年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

    In the previous study (Sate K.-I. et al. (1997) FEES Lett. 410, 136-140), we showed that the phosphorylation of Shc protein by c-Src is dependent on the binding of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to the PTB domain of Shc. In this study, we demonstrate that, in contrast to c-Src, v-Src and epidermal growth factor (EGF) receptor can phosphorylate Shc in a PtdIns(4,5)P2-independent manner and at different phosphorylation sites. To determine the phosphorylation sites in Shc, we used mutant Shc proteins in which tyrosine residues (Y) 317 and/or 239 and 240 were replaced by phenylalanine residues (F), We found that Y317F Shc but not Y239/240P or Y239/240/317F Shc was phosphorylated by c-Src. The reaction was PtdIns(4,5)P2-dependent and inhibited by the addition of PTB domain of Shc. On the other hand, v-Src and EGF receptor were able to phosphorylate both Y317F and Y239/240F but not Y239/240/317F Shc in a PtdIns (4,5)P2-independent manner. These results highlight the difference between c-Src and v-Src or EGF receptor and suggest that c-Src can phosphorylate predominantly on Tyr239/240 of Shc only when Shc PTB domain is bound to PtdIns(4,5)P2. (C) 1997 Academic Press.

    DOI： 10.1006/bbrc.1997.7667

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  • Phosphatidylinositol 4,5-bisphosphate stimulates phosphorylation of the adaptor protein Shc by c-Src 査読

    K Sato, H Yamamoto, T Otsuki, M Aoto, AA Tokmakov, F Hayashi, Y Fukami

    FEBS LETTERS   410 ( 2-3 )   136 - 140   1997年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

    The adaptor protein She was prepared as glutathione S-transferase fusion proteins (GST-Shc) and used as in vitro substrate for c-Src. Since phosphotyrosine-binding domain of She has been shown to bind phosphatidyl-inositol 4,5-bisphosphate (PtdIns(4,5)P2) [Zhou et al. (1995) Nature 378, 584-592], effect of PtdIns(4,5)P2 on the phosphorylation of GST-Shc by c-Src was examined, PtdIns(4,5)P2 stimulated the phosphorylation of GST-Shc without any effect on the c-Src activity as judged by both its autophosphorylation and phosphorylation of exogenous substrate, Cdc2 peptide. On the other hand, phosphatidylserine, phosphatidic acid, phosphatidylinositol, and phosphatidylinositol 4-phosphate but not phosphatidylcholine stimulated the c-Src activity itself. K-m for GST-Shc in the presence of 1 mu M PtdIns(4,5)P2 was calculated to be 90 nM. The PtdIns(4,5)P2-dependent phosphorylation of GST-Shc was inhibited by a GST-fusion protein containing the phosphotyrosine-binding domain of She. These results suggest that PtdIns(4,5)P2 can act as a regulator of phosphorylation of She by c-Src through its binding to She. (C) 1997 Federation of European Biochemical Societies.

    DOI： 10.1016/S0014-5793(97)00539-5

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  • Purification and characterization of a Src-related p57 protein-tyrosine kinase from Xenopus oocytes - Isolation of an inactive form of the enzyme and its activation and translocation upon fertilization 査読

    K Sato, M Aoto, K Mori, S Akasofu, AA Tokmakov, S Sahara, Y Fukami

    JOURNAL OF BIOLOGICAL CHEMISTRY   271 ( 22 )   13250 - 13257   1996年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    In the previous study (Fukami, Y., Sate, K.-I., Ikeda, H., Kamisango, K., Koizumi, K., and Matsuno, T. (1993) J. Biol. Chem. 268, 1132-1140), we found that an antibody termed anti-pepY antibody causes a severalfold activation of bovine brain c-Src. The anti-pepY antibody was raised against a synthetic peptide corresponding to residues 410-428 of chicken c-Src, one of the most conserved regions among the Src family protein-tyrosine kinases. In this study, we have used this antibody as an in vitro activator and purified a c-Src-related protein-tyrosine kinase from the particulate fraction of Xenopus laevis oocytes. A synthetic peptide corresponding to residues 7-26 of fission yeast Cdc2 was used as substrate. Immunoreactivity toward the antibody was also monitored during the purification. The purified kinase displayed a single polypeptide of 57 kDa on SDS-gel electrophoresis and showed a specific activity of 2.37 and 20.1 nmol/min/mg protein in the absence and the presence of the anti-pepY antibody, respectively. The purified enzyme underwent autophosphorylation and phosphorylated actin and the Cdc2 peptide exclusively on tyrosine residues. Specific antibodies against c-Src, Fyn, c-Yes, c-Fgr, Lck, Lyn, Hck, and Blk proteins did not recognize the p57 Xenopus tyrosine kinase. The kinase activity of the Xenopus enzyme was not affected by oocyte maturation but was found to be elevated severalfold upon fertilization. Fertilization also caused a translocation of the activated enzyme from the particulate fraction to the cytosolic fraction. The activation and translocation was observed within 1 min after fertilization. These results suggest a possible involvement of the p57 Xenopus tyrosine kinase in the signal transduction of fertilization.

    DOI： 10.1074/jbc.271.22.13250

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  • Biochemical evidence for the interaction of regulatory subunit of cAMP-dependent protein kinase with IDA (Inter-DFG-APE) region of catalytic subunit 査読

    S Sahara, K Sato, H Kaise, K Mori, A Sato, M Aoto, AA Tokmakov, Y Fukami

    FEBS LETTERS   384 ( 2 )   138 - 142   1996年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

    To explore the structural basis required for the holoenzyme formation of cAMP-dependent protein kinase, we have prepared rabbit anti-peptide antibodies that can block the holoenzyme formation without affecting the catalytic activity of the enzyme. The antibodies were raised against a specific site in the catalytic (C)-subunit, termed IDA (Inter-DFG-APE) region, which lies between the kinase subdomains VII and VIII. Although the C-subunit immunoprecipitated with anti-IDA antibodies could not form a stable complex with regulatory (R)-subunit, it was still susceptible to inhibition by the R-subunit or by PKI, a specific inhibitor peptide containing a pseudosubstrate site. These results indicate that there exists an IDA region-mediated interaction between the R- and C-subunits, which is distinct from that mediated through the substrate site and substrate binding site, In accordance with this idea, association of synthetic IDA peptides with the R-subunit was directly demonstrated by resonance mirror analysis, The calculated association constants of IDA peptides were high enough to suggest a possible involvement of the IDA region in the initial step of holoenzyme formation.

    DOI： 10.1016/0014-5793(96)00302-X

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  • C-SRC PHOSPHORYLATES EPIDERMAL GROWTH-FACTOR RECEPTOR ON TYROSINE-845 査読

    KI SATO, A SATO, M AOTO, Y FUKAMI

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   215 ( 3 )   1078 - 1087   1995年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

    In the previous study [Sato et al. (1995) Biochem. Biophys. Res. Commun. 210, 844-851], we found that c-Src was associated with epidermal growth factor (EGF) receptor and activated upon EGF treatment in A431 cells. In the present study, we investigated the phosphorylation of EGF receptor by c-Src in the c-Src-EGF receptor complex. We have focused our attention to tyrosine residue 845 (Y845) of EGF receptor as a candidate for the phosphorylation site. A synthetic peptide containing Y845, named Y845 peptide, which corresponds to residue 837 to 856 of EGF receptor, was found to be phosphorylated by c-Src and used to provide the standard phosphopeptide. In addition to the autophosphorylated peptide of 25 kDa, a phosphopeptide of 7 kDa was detected in the cyanogen bromide-digested fragments of the c-Src-associated EGF receptor phosphorylated in vitro in an EGF-dependent manner. In phosphopeptide mapping, tryptic digest of the 7-kDa phosphopeptide was shown to co-migrate with that of the phosphorylated Y845 peptide. The 7-kDa phosphopeptide was found to be phosphorylated exclusively on tyrosine. These results suggest that c-Src can phosphorylate EGF receptor on Y845 in an EGF-dependent manner. Furthermore, we confirmed that the same site of the c-Src-associatcd EGF receptor was phosphorylated in EGF-treated A431 cells. (C) 1995 Academic Press, Inc.

    DOI： 10.1006/bbrc.1995.2574

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  • SITE-SPECIFIC ASSOCIATION OF C-SRC WITH EPIDERMAL GROWTH-FACTOR RECEPTOR IN A431 CELLS 査読

    KI SATO, A SATO, M AOTO, Y FUKAMI

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   210 ( 3 )   844 - 851   1995年5月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We have examined the interaction between c-Src and epidermal growth factor (EGF) receptor in A431 cells. c-Src was found exclusively in the Triton X-100-solubilized particulate fraction and activated up to 3-fold within 1 min after EGF treatment of the cells. Association between c-Src and EGF receptor was detected by immunoprecipitation of c-Src followed by immunoblotting with anti-EGF receptor antibody. The c-Src-EGF receptor complex was found in both EGF-treated and untreated cells, but an augmented complex formation was observed in EGF-treated cells. We have isolated the complex by DEAE-cellulose column chromatography and found that a site-specific anti-c-Src antibody, which was raised against a synthetic peptide corresponding to residues 413 to 431 of human c-Src, did not recognize the c-Src protein in the complex, while other c-Src-specific antibodies tested did. Incubation of the complex with this synthetic peptide resulted in a partial dissociation of the complex. These results suggest that the specific region of c-Src is involved in the association with EGF receptor. (C) 1995 Academic Press, Inc.

    DOI： 10.1006/bbrc.1995.1735

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  • CHARACTERIZATION OF PROTEIN-KINASE-C IN XENOPUS OOCYTES 査読

    S SAHARA, K SATO, M AOTO, T OHNISHI, H KAISE, H KOIDE, K OGITA, Y FUKAMI

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   182 ( 1 )   105 - 114   1992年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI： 10.1016/S0006-291X(05)80118-4

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MISC

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講演・口頭発表等

  • Zinc finger protein 521欠損マウスの行動と脳モノアミンの解析

    大久保信孝, 平田香穂里, 青戸守, 安川正貴, 満田憲昭

    第68回日本生理学会中国四国地方会（岡山）  2016年11月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • 紅蔘由来サポニンの血管新生に与える影響

    青戸守, 満田憲昭, 大久保信孝, 昆和典

    第16回日本紅蔘研究会研究発表会  2017年3月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • 高麗人参由来サポニンの経口投与が酸化ストレスに対するマウス赤血球膜タンパク質に対する効果

    武智佳菜, 星野真子, 鈴木洋司, 大久保信孝, 青戸守, 寒川慶一, 満田憲昭

    第93回日本生理学会大会（札幌）  2016年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • ZFP521欠損マウス脳のモノアミン生合成の解析

    平田香穂里, 大久保信孝, 青戸守, 鈴木洋司, 満田憲昭

    第93回日本生理学会大会（札幌）  2016年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • マウス赤芽球脱核におけるサイクリンD3の役割

    坪内美菜, 三田佳夏子, 河野晋太郎, 鈴木洋司, 大久保信孝, 満田憲昭, 青戸守

    第93回日本生理学会大会（札幌）  2016年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • 血液保存による赤血球流動機能障害に対するデヒドロエピアンドロステロンの影響

    村上慶匡, 和泉遼, 福本健, 鈴木洋司, 大久保信孝, 青戸守, 満田憲昭

    第93回日本生理学会大会（札幌）  2016年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • デヒドロエピアンドロステロンが酸化ストレスによる赤血球レオロジー機能障害におよぼす影響

    和泉遼, 村上慶匡, 鈴木洋司, 大久保信孝, 青戸守, 満田憲昭

    第66回日本生理学会中国四国地方会（香川）  2014年11月 

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    記述言語：日本語   会議種別：口頭発表（基調）  

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  • 高麗人蔘由来の成分のマウスへの経口投与が赤血球膜タンパク質の酸化傷害に与える影響

    武智佳菜, 鈴木洋司, 大久保信孝, 寒川慶一, 青戸守, 満田憲昭

    第67回日本生理学会中国四国地方会（鳥取）  2015年10月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • Study of protective effect against oxidative stress on rheological disorder of erythrocyte

    和泉遼, 村上慶匡, 武智佳奈, 星野真子, 鈴木洋司, 大久保信孝, 青戸守, 満田憲昭

    第92回日本生理学会大会（神戸）  2015年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • 酸化ストレスに対する赤血球の防御機構に及ぼすリグナンの効果

    佐藤公俊, 岡田奈々枝, 鈴木洋司, 大久保信孝, 青戸守, 山内聡, 満田憲昭

    第91回日本生理学会大会（鹿児島）  2014年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • 酸化ストレスに対する保存赤血球の抗酸化機能への紅蔘由来サポニン分画の影響

    岡田奈々枝, 河野佑介, 和泉遼, 河野広貴, 鈴木洋司, 大久保信孝, 寒川慶一, 青戸守, 満田憲昭

    第91回日本生理学会大会（鹿児島）  2014年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • マウス赤芽球表面へのホスファチジルセリンの露出

    河野竜馬, 恩地裕史, 鈴木洋司, 大久保信孝, 満田憲昭, 青戸守

    第91回日本生理学会大会（鹿児島）  2014年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • 酸化ストレスによる赤血球流動機能障害に対するジヒドロエピアンドロステロンの効果

    和泉遼, 村上慶匡, 武智佳奈, 鈴木洋司, 大久保信孝, 青戸守, 満田憲昭

    第91回日本生理学会大会（鹿児島）  2014年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • Transferrin-Transferrin receptor 1 signaling is required for mouse erythroblast enucleation through the mechanism independent of iron uptake

    恩地裕史, 河野竜馬, 鈴木洋司, 大久保信孝, 辻本賀英, 満田憲昭, 青戸守

    第90回日本生理学会大会（東京）  2014年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • Transferrin-Transferrin receptor 1 signaling is required for mouse erythroblast enucleation through the mechanism independent of iron uptake

    青戸守, 恩地裕史, 河野竜馬, 鈴木洋司, 大久保信孝, 辻本賀英, 満田憲昭

    第36回日本分子生物学会大会  2013年12月 

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    記述言語：日本語   会議種別：ポスター発表  

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  • がん細胞による血管新生に対する紅蔘由来サポニン成分の効果

    第21回日本紅蔘研究会発表会  2022年3月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • マウス赤芽球の脱核時におけるCdk4-Cyclin D3複合体の役割

    三田佳夏子, 岩下晶穂, 大久保信孝, 満田憲昭, 青戸守

    第95回日本生理学会大会  2018年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • 紅蔘由来サポニン成分分画の血管新生に与える効果

    青戸守, 大久保信孝, 昆和典, 満田憲昭

    第17回日本紅蔘研究会研究発表会  2018年3月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • Zinc finger protein 521欠損マウスでは経腸吸収不良による発育不良があり、腸上皮肝細胞の分化異常の関与が示唆される

    大久保信孝, 森定なずな, 三宅琴音, 青戸守, 満田憲昭

    第70回日本生理学会中国四国地方会（愛媛）  2018年10月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • マウス赤芽球の脱核にはトランスフェリンートランスフェリン受容体１シグナルが必要であり、その機構は鉄の取り込みとは無関係である

    岩下晶穂, 三田佳夏子, 大久保信孝, 満田憲昭, 青戸守

    第95回日本生理学会大会  2018年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • Zinc finger protein 521欠損マウスで見られる行動異常はDopamine-beta-Hydroxylaseの上昇が関与する

    大久保信孝, 平田香穂里, 青戸守, 満田憲

    第69回日本生理学会中国四国地方会（徳島）  2017年10月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • 血液循環網形成に対する紅蔘成分の効果

    昆和典, 満田憲昭, 青戸守, 大久保信孝

    第20回日本紅蔘研究会発表会  2021年3月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • 紅蔘由来サポニン由来成分の血液循環網形成への効果

    青戸守, 満田憲昭, 大久保信孝, 昆和典

    第18回日本紅蔘研究会発表会  2019年3月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • マウス赤芽球の脱核過程におけるトランスフェリン受容体１の役割

    岩下晶穂, 三田佳夏子, 大久保信孝, 満田憲昭, 青戸守

    第70回日本生理学会中国四国地方会（愛媛）  2018年10月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • 紅蔘由来サポニン成分の 血液循環網形成への効果

    青戸 守, 大久保 信孝, 昆 和典, 満田 憲昭

    第19回日本紅蔘研究会発表会  2020年3月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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  • Zinc finger protein 521 involved in differentiation of intestinal stem cells and absorption. 国際会議

    Nazuna Morisada, Kotone Miyake, Mamoru Aoto, Noriaki Mitsuda, Nobutaka Ohkubo

    第9回アジア・オセアニア生理学会連合大会＆第96回日本生理学会合同大会  2019年3月 

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    記述言語：英語   会議種別：ポスター発表  

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  • 赤芽球脱核時における細胞周期制御機構の解析

    青戸守, 三田佳夏子, 岩下晶穂, 坪内美菜, 大久保信孝, 満田憲昭

    第68回日本生理学会中国四国地方会（岡山）  2016年11月 

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    記述言語：日本語   会議種別：口頭発表（一般）  

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共同研究・競争的資金等の研究課題

  • サルコペニア治療標的としてのRNA結合タンパク質Acin1の機能解析

    2022年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    青戸 守, 酒井 大史, 今井 祐記

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    配分額：4160000円 （ 直接経費：3200000円 、 間接経費：960000円 ）

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  • 血液循環網の形成に対する紅蔘由来サポニンの効果―がん細胞の生死を指標として―

    2022年4月 - 2023年3月

    日本紅蔘研究会  研究助成金 

    満田憲昭

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    担当区分：研究分担者 

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  • がん細胞による血管新生に対する紅蔘由来サポニン成分の効果

    2021年4月 - 2022年3月

    日本紅蔘研究会  研究助成金 

    満田憲昭

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    担当区分：研究分担者 

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  • 血液循環網の形成時における血管周皮細胞に対する紅蔘由来サポニン成分の効果

    2020年4月 - 2021年3月

    日本紅蔘研究会  研究助成金 

    満田憲昭

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    担当区分：研究分担者 

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  • 血管新生制御薬としての紅蔘由来成分の開発

    2019年4月 - 2020年3月

    日本紅蔘研究会  研究助成金 

    満田憲昭

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    資金種別：競争的資金

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  • アポリポ蛋白E受容体ファミリーを介した細胞死抑制機構-細胞内情報伝達経路の解明-

    2004年 - 2005年

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    満田 憲昭, 鈴木 洋司, 青戸 守, 前田 信治

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    配分額：3800000円 （ 直接経費：3800000円 ）

    研究の目的:申請者らはこれまでの研究において、星状膠細胞やミクログリアから分泌されるアポリポ蛋白E(ApoE)が神経細胞表面に存在するApoE受容体を介して神経細胞死を抑制していること、その経路にタウ蛋白リン酸化酵素GSK-3β活性の抑制が関与していることを報告した。そこで、本研究ではApoE受容体リガンドおよびApoE受容体の種類の違いによる細胞死抑制作用および細胞内情報伝達経路の相違を包括的に解析する。ApoE受容体リガンドとしては、今回ApoE以外にもリーリンを対象とする。
    結果:マウス胚性癌細胞(P19)にグルタミン酸負荷や血清の除去などにより細胞死を誘発させた。あらかじめ293T細胞を用いて発現させたApoE3、ApoE4、reelinを含む条件培地を加えておいたグループと、加えておかなかったグループ(対照群)とを比較したが、ApoEやreelinによる細胞死抑制効果は認められなかった。そこで、P19細胞をレチノイン酸処理することにより神経細胞様に分化させた後に同様の実験を行ったところ、ApoE3およびreelinに細胞死抑制効果が認められた。
    考察とまとめ:ApoE3やreelinの細胞死抑制効果は、P19細胞をそのまま用いた場合には認められず、神経細胞様に分化させたP19細胞の場合には認められた。このように神経細胞様に分化することによって細胞死抑制効果が増強されるメカニズムとして、細胞でのアポE受容体の発現誘導が関係している可能性がある。アポE受容体の種類および発現量の違いによる定量的な解析をさらに続けていく。

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担当経験のある科目（授業）

  • 疾病治療論Ⅰ、疾病治療論Ⅱ

    2013年4月 - 現在 機関名：河原医療大学校 看護学科

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  • 基礎医学展望Ⅱ

    2010年4月 - 現在 機関名：愛媛大学医学部医学科

    　詳細を見る

  • 人体生理学講義

    2004年4月 - 現在 機関名：愛媛大学医学部医学科

    　詳細を見る

  • 人体生理学実習

    2003年10月 - 現在 機関名：愛媛大学医学部医学科

    　詳細を見る

  • 生体機能学Ⅱ

    2023年11月 - 現在 機関名：聖カタリナ大学

    　詳細を見る

  • 基礎研究方法論

    2017年4月 - 現在 機関名：愛媛大学大学院医学系研究科

    　詳細を見る

  • 生理学Ⅱ

    2005年4月 - 2006年9月 機関名：愛媛十全医療学院

    　詳細を見る

  • 解剖生理学

    2004年4月 - 現在 機関名：愛媛県消防学校

    　詳細を見る

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