Molecular and physiological functions of NDRG1 and NDRG4

2012 Fiscal Year Final Research Report

• Project/Area Number: 22570151
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: KOKAME Koichi 独立行政法人国立循環器病研究センター, 研究所, 室長 (40270730)
• Co-Investigator(Renkei-kenkyūsha): IMOTO Hitomi (YAMAMOTO Hitomi) 独立行政法人国立循環器病研究センター, 研究所, 非常勤研究員 (50532230)
• Project Period (FY): 2010 – 2012
• Keywords: タンパク質 / 脳機能 / 心機能 / 神経細胞 / NDRG1 / NDRG4 / BDNF

Research Abstract

We previously generated NDRG4-deficient mice that exhibit spatial learning deficits and vulnerabilities to cerebral ischemia. This study revealed that NDRG4 contributed to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the normal functions of neuronal cells. We identified NDRG4-binding proteins, which also interacted with NDRG1-NDRG3. NDRG family proteins may regulate cell activities through the functions of the binding proteins.

Research Products

• [Journal Article] ADAMTS13 activity and genetic mutations in Japanese subjects. (2013)
  • Author(s): Toshiyuki Miyata, Koichi Kokame, Masanori Matsumoto, and Yoshihiro Fujimura.
  • Journal Title: Haemostaselolgie Volume: 33 Pages: 131-137
  • DOI: DOI:10.5482/HAMO-12-11-0017
  • Peer Reviewed
• [Journal Article] ADAMTS13 safeguards the myocardium in a mouse model of acute myocardial infarction. (2012)
  • Author(s): Masaaki Doi, Hideto Matsui, Yukiji Takeda, Yoshihiko Saito, Maiko Takeda, Yasunori Matsunari, Kenji Nishio, Midori Shima, Fumiaki Banno, Masashi Akiyama, Koichi Kokame, Toshiyuki Miyata, and Mitsuhiko Sugimoto.
  • Journal Title: Thromb. Haemost. Volume: 108 Pages: 1236-1238
  • DOI: DOI:10.1160/TH12-09-0674
  • Peer Reviewed
• [Journal Article] Binding of von Willebrand factor cleaving protease ADAMTS13 to Lys-plasmin(ogen). (2012)
  • Author(s): Yongchol Shin, Masashi Akiyama, Koichi Kokame, Kenji Soejima, and Toshiyuki Miyata.
  • Journal Title: J. Biochem. Volume: 152 Pages: 251-25
  • DOI: DOI:10.1093/jb/mvs066
  • Peer Reviewed
• [Journal Article] STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein. (2012)
  • Author(s): Takashi Sato, Yasuhiro Sako, Misato Sho, Mamiko Momohara, Mary Ann Suico, Tsuyoshi Shuto, Hideki Nishitoh, Tsukasa Okiyoneda, Koichi Kokame, Masayuki Kaneko, Manabu Taura, Masanori Miyata, Keisuke Chosa, Tomoaki Koga, Saori Morino-Koga, Ikuo Wada, and Hirofumi Kai.
  • Journal Title: Mol. Cell Volume: 47 Pages: 99-110
  • DOI: DOI:10.1016/j.molcel.2012.04.015
  • Peer Reviewed
• [Journal Article] Derlin-l deficiency is embryonic lethal, Derlin-3 deficiency appears normal, and Herp deficiency is intolerant to glucose load and ischemia in mice. (2012)
  • Author(s): Yuka Eura, Hiroji Yanamoto, Yuji Arai, Tomohiko Okuda, Toshiyuki Miyata, and Koichi Kokame.
  • Journal Title: PLoS One Volume: 7 Pages: e34298
  • DOI: DOI:10.1371/journal.pone.0034298
  • Peer Reviewed
• [Journal Article] ADAMTS13 gene deletion enhances plasma high-mobility group boxl elevation and neuroinf lamination in brain ischemia-reperfusion injury. (2012)
  • Author(s): Masayuki Fujioka, Takafumi Nakano, Kazuhide Hayakawa, Keiichi Irie, Yoshiharu Akitake, Yuya Sakamoto, Kenichi Mishima, Carl Muroi, Yasuhiro Yonekawa, Fumiaki Banno, Koichi Kokame, Toshiyuki Miyata, Kenji Nishio, Kazuo Okuchi, Katsunori Iwasaki, Michihiro Fujiwara, and Bo K. Siesjo
  • Journal Title: Neurol. Sci. Volume: 33 Pages: 1107-1115
  • DOI: DOI:10.1007/s10072-011-0913-9
  • Peer Reviewed
• [Journal Article] 小胞体ストレスと循環器疾患 (2012)
  • Author(s): 小亀浩市・宮田敏行
  • Journal Title: 生体の科学 Volume: 33 Pages: 390-391
  • URL: http://www.igaku-shoin.co.jp/journalDetai1.do?journal=34660
• [Journal Article] ADAMTS13研究の最先端 (2012)
  • Author(s): 宮田敏行・小亀浩市・秋山正志・坂野史明・中山大輔・武田壮一
  • Journal Title: 臨床血液 Volume: 53 Pages: 672-679
  • DOI: DOI:10.11406/rinketsu.53.672
• [Journal Article] Genetic analysis of patients with deep vein thrombosis during pregnancy and postpartum. (2011)
  • Author(s): Reiko Neki, Tomio Fujita, Koichi Kokame, Isao Nakanishi, Masako Waguri, Yuzo Imayoshi, Noriyuki Suehara, Tomoaki Ikeda, and Toshiyuki Miyata.
  • Journal Title: Int. J. Hematol. Volume: 94 Pages: 150-155
  • DOI: DOI:10.1007/s12185-011-0902-z
  • Peer Reviewed
• [Journal Article] The effect of Ndrg2 expression on astroglial activation. (2011)
  • Author(s): Toshiaki Takeichi, Mika Takarada-Iemata, Koji Hashida, Hirofumi Sudo, Tomohiko Okuda, Koichi Kokame, Taku Hatano, Masashi Takanashi, Sayaka Funabe, Nobutaka Hattori, Osamu Kitamura, Yasuko Kitao, and Osamu Hori.
  • Journal Title: Neurochem. Int. Volume: 59 Pages: 21-27
  • DOI: DOI:10.1016/j.neuint.2011.03.019
  • Peer Reviewed
• [Journal Article] Polymorphisms and mutations of ADAMTS13 in Japanese population and estimation of the number of patients with Upshaw-Schulman syndrome. (2011)
  • Author(s): Koichi Kokame, Yoshihiro Kokubo, and Toshiyuki Miyata.
  • Journal Title: J. Thromb. Haemost. Volume: 9 Pages: 1654-1656
  • DOI: DOI:10.1111/j.1538-7836.2011.04399.x
  • Peer Reviewed
• [Journal Article] NDRG4 protein-deficient mice exhibit spatial learning deficits and vulnerabilities to cerebral ischemia. (2011)
  • Author(s): Hitomi Yamamoto, Koichi Kokame, Tomohiko Okuda, Yukako Nakajo, Hiroji Yanamoto, and Toshiyuki Miyata.
  • Journal Title: J. Biol. Chem. Volume: 286 Pages: 26158-26165
  • DOI: DOI:10.1074/jbc.Mi11.256446
  • Peer Reviewed
• [Journal Article] Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. (2011)
  • Author(s): Yoshihiro Fujimura, Masanori Matsumoto, Ayami Isonishi, Hideo Yagi, Koichi Kokame, Kenji Soejima, Mitsuru Murata, and Toshiyuki Miyata.
  • Journal Title: J. Thromb. Haemost. Volume: 9(Suppl. 1) Pages: 283-301
  • DOI: DOI:10.1111/j.1538-7836.2011.04341.x
  • Peer Reviewed
• [Journal Article] ER-stress-inducible Herp, facilitates the degradation of immature nicastrin. (2011)
  • Author(s): Toshihiro Marutani, Tomoji Maeda, Chiaki Tanabe, Kun Zou, Wataru Araki, Koichi Kokame, Makoto Michikawa, and Hiroto Komano.
  • Journal Title: Biochim. Biophys. Acta-General Subjects Volume: 1810 Pages: 790-798
  • DOI: DOI:10.1016/j.bbagen.2011.04.017
  • Peer Reviewed
• [Journal Article] von Willebrand factor-to-ADAMTS13 ratio increases with age in a Japanese population. (2011)
  • Author(s): Koichi Kokame, Toshiyuki Sakata, Yoshihiro Kokubo, and Toshiyuki Miyata.
  • Journal Title: J. Thromb. Haemost. Volume: 9 Pages: 1426-1428
  • DOI: DOI:10.1111/j.1538-7836.2011.04333.x
  • Peer Reviewed
• [Journal Article] Gene and protein analysis of brain derived neurotrophic factor expression in relation to neurological recovery induced by an enriched environment in a rat stroke model. (2011)
  • Author(s): Kenji Hirata, Yuji Kuge, Chiaki Yokota, Akina Harada, Koichi Kokame, Hiroyasu Inoue, Hidekazu Kawashima, Hiroko Hanzawa, Yuji Shono, Hideo Saji, Kazuo Minematsu, and Nagara Tamaki.
  • Journal Title: Neurosci. Lett. Volume: 495 Pages: 210-215
  • DOI: DOI:10.1016/j.neulet.2011.03.068
  • Peer Reviewed
• [Journal Article] Light-dependent and circadian clock-regulated activation of SREBP, XBP1 and HSF pathways in the pineal gland. (2011)
  • Author(s): Megumi Hatori, Tsuyoshi Hirota, Michiko Iitsuka, Nobuhiro Kurabayashi, Shogo Haraguchi, Koichi Kokame, Ryuichiro Sato, Akira Nakai, Toshiyuki Miyata, Kazuyoshi Tsutsui, and Yoshitaka Fukada.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 108 Pages: 4864-4869
  • DOI: DOI:10.1073/pnas.1015959108
  • Peer Reviewed
• [Journal Article] Gene expression associated with an enriched environment after transient focal ischemia. (2011)
  • Author(s): Yuji Shono, Chiaki Yokota, Yuji Kuge, Shinsuke Kido, Akina Harada, Koichi Kokame, Hiroyasu Inoue, Mariko Hotta, Kenji Hirata, Hideo Saji, Nagara Tamaki, and Kazuo Minematsu.
  • Journal Title: Brain Res. Volume: 1376 Pages: 60-65
  • DOI: DOI:10.1016/j.brainres.2010.12.058
  • Peer Reviewed
• [Journal Article] 日本人のADAMTS13 (2011)
  • Author(s): 小亀浩市
  • Journal Title: 日本血栓止血学会誌 Volume: 22 Pages: 368-373
  • DOI: DOI:10.2491/jjsth.22.368
• [Journal Article] Deletion of Herp facilitates degradation of cytosolic proteins. (2010)
  • Author(s): Hikari Miura, Koji Hashida, Hirofumi Sudo, Yoshitaka Awa, Mika Takarada-Iemata, Koichi Kokame, Tetsuya Takahashi, Masayasu Matsumoto, Yasuko Kitao, and Osamu Hori.
  • Journal Title: Genes Cells Volume: 15 Pages: 843-853
  • DOI: DOI:10.1111/j.1365-2443.2010.01422.x
  • Peer Reviewed
• [Journal Article] WF切断酵素ADAMTS13のエキソサイト認識機構 (2010)
  • Author(s): 秋山正志・武田壮一・小亀浩市・高木淳一・宮田敏行
  • Journal Title: 生化学 Volume: 82 Pages: 950-956
  • URL: http://www.jbsoc.or.jp/event/magazine/pdf/82-10-05.pdf
• [Journal Article] Upregulation of eNOS, SIRT1, and autophagy-related genes by repeated treatment with resveratrol in human umbilical vein endothelial cells.
  • Author(s): Yoshie Takizawa, Yukiko Kosuge, Hiroyo Awaji, Emi Tamura, Ayako Takai, Takaaki Yanai, Reiko Yamamoto, Koichi Kokame, Toshiyuki Miyata, Rieko Nakata, and Hiroyasu Inoue.
  • Journal Title: Brit. J. Nutr. Volume: (In press) Pages: PMID:23750556
  • Peer Reviewed
• [Journal Article] Crystal structure and enzymatic activity of an ADAMTS13 mutant with the East Asian-specific P475S polymorphism.
  • Author(s): Masashi Akiyama, Daisuke Nakayama, Soichi Takeda, Koichi Kokame, Junichi Takagi, and Toshiyuki Miyata.
  • Journal Title: J. Thromb. Haemost. Volume: (In press)
  • DOI: DOI:10.1111/jth.12279
  • Peer Reviewed
• [Presentation] 脳と心臓に特異的に発現する細胞内タンパク質NDRG4はNa^+/K^+-ATPase α3サブユニットに結合する (2012)
  • Author(s): 井本(山本)ひとみ・宮田敏行・小亀浩市
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 20121214-16
• [Presentation] 日本人の遺伝的血栓性リスクを有するモデルマウスの作製と解析 (2012)
  • Author(s): 坂野史明・喜多俊行・柳本広二・小亀浩市・宮田敏行
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 20121214-16
• [Presentation] Protective Role of ADAMTS13 for Myocardium in Mouse Model of Experimental Myocardial Infarction. (2012)
  • Author(s): Masaaki Doi, Hideto Matsui, Yukiji Takeda, Yoshihiko Saito, Maiko Takeda, Yasunori Matsunari, Kenji Nishio, Midori Shima, Fumiaki Banno, Masashi Akiyama, Koichi Kokame, Toshiyuki Miyata, and Mitsuhiko Sugimoto.
  • Organizer: 2012 ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20121208-11
• [Presentation] Gene mutation analysis for Upshaw-Schulman syndrome. (2012)
  • Author(s): Koichi Kokame.
  • Organizer: The 58th Annual Scientific and Standardization Committee Meeting
  • Place of Presentation: Liverpool, UK
  • Year and Date: 20120627-30
• [Presentation] ハイドロダイナミクス法によるin vivo遺伝子導入を用いたERAD基質の解析 (2011)
  • Author(s): 樋口(江浦)由佳・宮田敏行・小亀浩市
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. (2011)
  • Author(s): Yoshihiro Fujimura, Masanori Matsumoto, Ayami Isonishi, Koichi Kokame, Kenji Soejima, Mitsuru Murata, and Toshiyuki Miyata.
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-16
• [Presentation] SATB1 induces early lymphocyte differentiation from primitive hematopoietic progenitors. (2011)
  • Author(s): Yusuke Satoh, Takafumi Yokota, Hirokazu Tanaka, Koichi Kokame, Toshiyuki Miyata, Itaru Matsumura, Kenji Oritani, and Yuzuru Kanakura.
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] ADAMTS13研究の最先端 (2011)
  • Author(s): 宮田敏行・小亀浩市・秋山正志・武田壮一・坂野史明
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] P475S型ADAMTS13タンパク質の部分立体構造決定 (2011)
  • Author(s): 秋山正志・中山大輔・武田壮一・小亀浩市・高木淳一・宮田敏行
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] NDRG4は大脳皮質中のBDNF量を正常に保ち,記憶学習能力の維持作用と虚血性脳卒中に対する脳保護作用を示す (2011)
  • Author(s): 井本(山本)ひとみ・小亀浩市・奥田智彦・中城有香子・柳本広二・宮田敏行
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] NDRG4欠損マウスは,大脳皮質BDNF量の低下とともに,記憶学習能力の低下と局所脳虚血による梗塞巣の増大を示す (2011)
  • Author(s): 井本(山本)ひとみ・小亀浩市・奥田智彦・中城有香子・柳本広二・宮田敏行
  • Organizer: 第9回血液・血管オルビス
  • Place of Presentation: 東京
  • Year and Date: 2011-08-20
• [Presentation] NDRG4-deficient mice exhibit spatial learning deficits and vulnerabilities to cerebral ischemia with the decreased level of BDNF in the cortex. (2011)
  • Author(s): Hitomi Yamamoto, Koichi Kokame, Tomohiko Okuda, Yukako Nakajo, Hiroji Yanamoto, and Toshiyuki Miyata
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Kyoto
  • Year and Date: 2011-07-28
• [Presentation] Generation of knock-in mice carrying a K196E point mutation in protein S. (2011)
  • Author(s): Fumiaki Banno, Toshiyuki Kita, Hiroji Yanamoto, Koichi Kokame, Koji Iihara, and Toshiyuki Miyata
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Kyoto
  • Year and Date: 2011-07-27
• [Presentation] Estimation of the number of individuals with a congenital ADAMTS13 deficiency in Japan. (2011)
  • Author(s): Koichi Kokame, Yoshihiro Kokubo, and Toshiyuki Miyata
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Kyoto
  • Year and Date: 2011-07-25
• [Presentation] Findings from ADAMTS13 activity assay. (2011)
  • Author(s): Koichi Kokame
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Kyoto
  • Year and Date: 2011-07-25
• [Presentation] Roles of ERAD molecule Herp in the Parkinson' s disease (PD) models. (2010)
  • Author(s): Hirofumi Sudo, Mika Takarada-Iemata, Koji Hashida, Koichi Kokame, Yasuko Kitao, Osamu Hori.
  • Organizer: 第33回日本神経科学大会・第53回日本神経科学会大会・第20回日本神経回路学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20100902-04
• [Presentation] Derlin-1 and Derlin-2 but not Derlin-3 deficient mice were embryonic lethal. (2010)
  • Author(s): Yuka Eura, Yuji Arai, Toshiyuki Miyata, and Koichi Kokame.
  • Organizer: 50th ASCB Annual Meeting, Philadelphia
  • Place of Presentation: USA
  • Year and Date: 2010-12-14
• [Presentation] 小胞体関連分解(ERAD)因子の発現量は臓器依存的に調節されておりDerlin-3欠損の影響を受ける (2010)
  • Author(s): 樋口(江浦)由佳・宮田敏行・小亀浩市
  • Organizer: 第83回日本生化学会大会,第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 脳虚血後の環境刺激による神経機能回復においてproBDNFの関与は小さい (2010)
  • Author(s): 平田健司・久下裕司・横田千晶・生野雄二・小亀浩市・原田晃名・半渾宏子・河嶋秀和・佐治英郎・峰松一夫・玉木長良
  • Organizer: 第22回日本脳循環代謝学会総会
  • Place of Presentation: 豊中
  • Year and Date: 2010-11-26
• [Presentation] Structure and function of TTP-related metalloprotease ADAMTS13. (2010)
  • Author(s): Koichi Kokame
  • Organizer: The 6th Congress of Asia Pacific Society on Thrombosis and Haemostasis (APSTH 2010),
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2010-10-15
• [Presentation] 小胞体関連分解(ERAD)で機能する膜タンパク質Herpの欠損は耐糖能と虚血耐性の低下につながる (2010)
  • Author(s): 樋口(江浦)由佳・宮田敏行・小亀浩市
  • Organizer: 第8回血液・血管オルビス
  • Place of Presentation: 東京
  • Year and Date: 2010-08-21
• [Presentation] Fluorogenic and chromogenic assays of ADAMTS13 activity. (2010)
  • Author(s): Koichi Kokame
  • Organizer: The 56th Annual Scientific and Standardization Committee Meeting
  • Place of Presentation: Cairo, Egypt
  • Year and Date: 2010-05-24
• [Presentation] ADAMTS13の基準値と遺伝子多型 (2010)
  • Author(s): 小亀浩市
  • Organizer: 第7回日本血栓止血学会sscシンポジウーム
  • Place of Presentation: 東京
  • Year and Date: 2010-01-12
• [Remarks]
  • URL: http://www.ncvc.go.jp/res/divisions/etiology/index,html