研究者データベース

加藤 いづみ(カトウ イヅミ)
薬学研究院 臨床薬学教育研究センター
助教

基本情報

所属

  • 薬学研究院 臨床薬学教育研究センター

職名

  • 助教

学位

  • 博士(生命科学)(北海道大学)

J-Global ID

研究キーワード

  • 細胞生物学   創薬スクリーニング   分子間相互作用   酸化ストレス   包括脳ネットワーク   

研究分野

  • ライフサイエンス / 機能生物化学

職歴

  • 2018年04月 - 現在 北海道大学 薬学研究院 臨床薬学教育研究センター
  • 2012年04月 - 2018年03月 北海道大学 大学院薬学研究院 創薬科学研究教育センター

研究活動情報

論文

  • Yoichiro Fujioka, Shinya Nishide, Toyoyuki Ose, Tadaki Suzuki, Izumi Kato, Hideo Fukuhara, Mari Fujioka, Kosui Horiuchi, Aya O Satoh, Prabha Nepal, Sayaka Kashiwagi, Jing Wang, Mika Horiguchi, Yuko Sato, Sarad Paudel, Asuka Nanbo, Tadaaki Miyazaki, Hideki Hasegawa, Katsumi Maenaka, Yusuke Ohba
    Cell host & microbe 23 6 809 - 818 2018年06月13日 [査読有り][通常論文]
     
    Influenza A virus (IAV) infection is initiated by the attachment of the viral glycoprotein hemagglutinin (HA) to sialic acid on the host cell surface. However, the sialic acid-containing receptor crucial for IAV infection has remained unidentified. Here, we show that HA binds to the voltage-dependent Ca2+ channel Cav1.2 to trigger intracellular Ca2+ oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca2+ channel blockers (CCBs) or by knockdown of Cav1.2. The CCB diltiazem also inhibited virus replication in vivo. Reintroduction of wild-type but not the glycosylation-deficient mutants of Cav1.2 restored Ca2+ oscillations and virus infection in Cav1.2-depleted cells, demonstrating the significance of Cav1.2 sialylation. Taken together, we identify Cav1.2 as a sialylated host cell surface receptor that binds HA and is critical for IAV entry.
  • Takuya Yamane, Izumi Kato-Ose, Tatsuji Sakamoto, Yoshihisa Nakano
    Open Biochem. J. 12 29 - 35 2018年 [査読有り]
     
    Background: Asparaginyl endopeptidase, also known as legumain (EC 3.4.22.34) shows strong activity in the mouse kidney. Legumain is also highly expressed in tumors. DJ-1/PARK7 is a Parkinson's disease- and cancer-associated protein. DJ-1 is a coactivator of various transcription factors. Recently, we reported that transcription of the legumain gene is regulated by p53 through DJ-1. Methods: We measured the secretion levels of legumain in a conditioned medium of DJ-1 knockout cells and in serum from DJ-1 knockout mice using Western blotting and ELISA. We performed immunocytochemical staining of legumain to examine the localization of legumain in DJ-1-knockout cells. Results: We found that the secretion levels of legumain were increased in the conditioned medium of DJ-1-knockout cells and in serum from DJ-1-knockout mice. Dot structures of legumain were also increased in DJ-1-knockout cells. Conclusion: The results suggest that legumain secretion from DJ-1-knockout cells and in mice increases through its increased expression and accumulation in membrane-associated vesicles.
  • Kazuko Takahashi-Niki, Yoko Ganaha, Takeshi Niki, Shota Nakagawa, Izumi Kato-Ose, Sanae M. M. Iguchi-Ariga, Hiroyoshi Ariga
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 474 1 131 - 136 2016年05月 [査読有り][通常論文]
     
    The DJ-1 gene is a ras-dependent oncogene and also a causative gene for a familial form of Parkinson's disease park7. DJ-1 is a multi-functional protein and plays roles in regulation of cell growth, cells death, metabolism and mitochondrial homeostasis against oxidative stress. To explore various functions, DJ-1 associates with a number of proteins localized in the nucleus, cytoplasm and mitochondria. The oxidative status of a cysteine residue at an amino acid number 106 (C106) of DJ-1 determines the active level of DJ-1. Precise molecular mechanism of exploration of DJ-1 function is, however, not resolved. In this study, we identified Sirtuin family proteins (SIRT1, 2, and 4-6) as DJ-1-binding proteins, and DJ-1 associated with SIRT1 in cells. Sirtuins like DJ-1 also regulates growth, death and metabolism of cells and mitochondrial homeostasis. We found that DJ-1 stimulated deacetylase activity of SIRT1 and that SIRT1-suppressed transcriptional activity of SIRT1-target p53 was further decreased by DJ-1. Furthermore, SIRT1 activity was reduced in DJ-1-knockout cells, and this reduced activity was restored by reintroduction of wild-type DJ-1 but not of C106-mutant DJ-I into DJ-1-knockout cells. It is first report showing direct connection of DJ-1 with SIRT1. (C) 2016 Elsevier Inc. All rights reserved.
  • Kazuko Takahashi-Niki, Izumi Kato-Ose, Hiroaki Murata, Hiroshi Maita, Sanae M. M. Iguchi-Ariga, Hiroyoshi Ariga
    JOURNAL OF BIOLOGICAL CHEMISTRY 290 29 17838 - 17847 2015年07月 [査読有り][通常論文]
     
    DJ-1 is an oncogene and also a causative gene for familial Parkinson disease. DJ-1 has various functions, and the oxidative status of cysteine at position 106 (Cys-106) is crucial for determination of the activation level of DJ-1. Although DJ-1 requires activated Ras for its oncogenic activity and although it activates the extracellular signal-regulated kinase (ERK) pathway, a cell growth pathway downstream of Ras, the precise mechanism underlying activation of the ERK pathway by DJ-1 is still not known. In this study, we found that DJ-1 directly bound to the kinase domain of c-Raf but not to Ras and that Cys-106 mutant DJ-1 bound to c-Raf more weakly than did wild-type DJ-1. Co-localization of DJ-1 with c-Raf in the cytoplasm was enhanced in epidermal growth factor (EGF)-treated cells. Knockdown of DJ-1 expression attenuated the phosphorylation level of c-Raf in EGF-treated cells, resulting in reduced activation of MEK and ERK1/2. Although EGF-treated DJ-1 knock-out cells also showed attenuated c-Raf activation, reintroduction of wild-type DJ-1, but not C106S DJ-1, into DJ-1 knock-out cells restored c-Raf activation in a DJ-1 binding activity in a c-Raf-dependent manner. DJ-1 was not responsible for activation of c-Raf in phorbol myristate acetate-treated cells. Furthermore, DJ-1 stimulated self-phosphorylation activity of c-Raf in vitro, but DJ-1 was not a target for Raf kinase. Oxidation of Cys-106 in DJ-1 was not affected by EGF treatment. These findings showed that DJ-1 is a positive regulator of the EGF/Ras/ERK pathway through targeting c-Raf.
  • Takuya Yamane, Sato Murao, Izumi Kato-Ose, Lisa Kashima, Motoki Yuguchi, Miyuki Kozuka, Keisuke Takeuchi, Hisakazu Ogita, Iwao Ohkubo, Hiroyoshi Ariga
    Biochemical and Biophysical Research Communications 438 4 613 - 618 2013年09月06日 [査読有り][通常論文]
     
    Legumain (EC 3.4.22.34) is an asparaginyl endopeptidase. Strong legumain activity was observed in the mouse kidney, and legumain was found to be highly expressed in tumors. We previously reported that bovine kidney annexin A2 was co-purified with legumain and that legumain cleaved the N-terminal region of annexin A2 at an Asn residue in vitro and in vivo. In this study, we found a p53-binding site in intron 1 of the human legumain gene using computational analysis. To determine whether transcription of the legumain gene is regulated by p53, HCT116 cells were transfected with p53 siRNA and the effect of knockdown of p53 expression on legumain expression was examined. The results showed that expression levels of both legumain mRNA and protein were decreased in the siRNA-treated cells. Furthermore, enzyme activity of legumain was also increased by doxorubicin and its activity was reduced by knockdown of p53 in HCT116 cells. These results suggest that legumain expression and its enzyme activity are regulated by p53. © 2013 Elsevier Inc.
  • Identification of DJ-1-associated regions on human genes from SH-SY5Y cells using chromatin immunoprecipitation sequence technique
    Takuya Yamane, Naoyuki Sugimoto, Hiroshi Maita, Kazufumi Watanabe, Kazuko Takahashi-Niki, Chinatsu Maita, Izumi Kato-Ose, Shizuma Ishikawa, Jian-Wei Gao, Hirotake Kitaura, Takeshi Niki, Sanae M.M. Iguchi-Ariga, Hiroyoshi Ariga
    Mol. Biol. 3 15 2013年 [査読有り][通常論文]
  • Izumi Kato, Hiroshi Maita, Kazuko Takahashi-Niki, Yoshiro Saito, Noriko Noguchi, Sanae M. M. Iguchi-Ariga, Hiroyoshi Ariga
    MOLECULAR AND CELLULAR BIOLOGY 33 2 340 - 359 2013年01月 [査読有り][通常論文]
     
    DJ-1 is an oncogene and the causative gene for familial Parkinson's disease. Although the oxidative status of DJ-1 at cysteine 106 (C106) is thought to affect all of the activities of DJ-1 and excess oxidation leads to the onset of various diseases, the precise molecular mechanisms underlying the effects of oxidation of DJ-1 on protein-protein interactions of DJ-1 remain unclear. In this study, we found that DJ-1 bound to the DNA-binding region of p53 in a manner dependent on the oxidation of C106. Of the p53 target genes, the expression level and promoter activity of the DUSP1 gene, but not those of the p21 gene, were increased in H2O2-treated DJ-1(-/-) cells and were decreased in wild-type DJ-1- but not C106S DJ-1-transfected H1299 cells through sequestration of p53 from the DUSP1 promoter by DJ-1. DUSP1 downregulated by oxidized DJ-1 activated extracellular signal-regulated kinase (ERK) and decreased apoptosis. The DUSP1 and p21 promoters harbor nonconsensus and consensus p53 recognition sequences, respectively, which have low affinity and high affinity for p53. However, DJ-1 inhibited p21 promoter activity exhibited by p53 mutants harboring low DNA-binding affinity but not by wild-type p53. These results indicate that DJ-1 inhibits the expression of p53 target genes and depend on p53 DNA-binding affinity and oxidation of DJ-1 C106.
  • Hiroyoshi Ariga, Kazuko Takahashi-Niki, Izumi Kato, Hiroshi Maita, Takeshi Niki, Sanae M. M. Iguchi-Ariga
    Oxidative Medicine and Cellular Longevity 2013 683920  2013年 [査読有り][通常論文]
     
    Parkinson's disease (PD) is caused by dopaminergic neuronal death in the substantia nigra, resulting in a reduced level of dopamine in the striatum. Oxidative stress and mitochondrial dysfunction are thought to be major causes of neurodegeneration in PD. Although genetic and environmental factors are thought to affect the onset of PD, precise mechanisms at the molecular level have not been elucidated. The DJ-1 gene is a causative gene for familial PD (park7) and also an oncogene. DJ-1 has various functions, including transcriptional regulation, antioxidative stress reaction, and chaperone, protease, and mitochondrial regulation, and its activity is regulated by its oxidative status, especially that of cysteine 106 (C106) of DJ-1. Excess oxidation of DJ-1, which renders DJ-1 inactive, has been observed in patients with sporadic PD and Alzheimer's disease, suggesting that DJ-1 also participates in the onset and pathogenesis of sporadic PD as well as familial PD. DJ-1 is also a stress sensor and its expression is increased upon various stresses, including oxidative stress. In this review, we describe functions of DJ-1 against oxidative stress and possible roles of DJ-1 in the pathogenesis of PD. © 2013 Hiroyoshi Ariga et al.
  • Shiori Yamaguchi, Takuya Yamane, Kazuko Takahashi-Niki, Izumi Kato, Takeshi Niki, Matthew S. Goldberg, Jie Shen, Kenji Ishimoto, Takefumi Doi, Sanae M. M. Iguchi-Ariga, Hiroyoshi Ariga
    PLOS ONE 7 5 e38144  2012年05月 [査読有り][通常論文]
     
    DJ-1 is a novel oncogene and also causative gene for familial Parkinson's disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene.

その他活動・業績

  • インフルエンザウイルス細胞侵入において鍵となる宿主タンパク質の同定
    藤岡 容一朗, 西出 真也, 尾瀬 農之, 加藤 いづみ, 福原 秀雄, 藤岡 真理, 堀内 浩水, 佐藤 絢, Nepal Prabha, 柏木 彩花, Wang Jing, 堀口 美香, Paudel Sarad, 南保 明日香, 宮崎 忠昭, 前仲 勝実, 大場 雄介 日本細胞生物学会大会講演要旨集 69回 61 -61 2017年05月 [査読無し][通常論文]
  • 藤岡容一朗, 西出真也, 尾瀬農之, 加藤いづみ, 福原秀雄, 藤岡真理, 堀内浩水, 佐藤絢, NEPAL Prabha, 柏木彩花, WANG Jing, 堀口美香, PAUDEL Sarad, 南保明日香, 宮崎忠昭, 前仲勝実, 前仲勝実, 大場雄介 日本細胞生物学会大会(Web) 69th ROMBUNNO.T8‐04(P2‐028) (WEB ONLY) -61 2017年05月 [査読無し][通常論文]
  • Izumi Kato, Hiroshi Maita, Sanae M. M. Iguchi-Ariga, Hiroyoshi Ariga NEUROSCIENCE RESEARCH 68 E307 -E307 2010年 [査読無し][通常論文]

教育活動情報

主要な担当授業

  • 臨床薬学事前演習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 共?試験、CBT、在宅医療、災害時医療
  • OSCE対応演習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 客観的臨床能力試験(OSCE)
  • 実務実習事前実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 実務実習,調剤,医療面接,服薬指導,無菌操作,フィジカルアセスメント
  • 分析化学実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 定量分析,状態分析,日本薬局方


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