Proteomic investigation of oxidized proteins in cerebrospinal fluid for developing novel biomarkers of Alzheimer's disease.

2012 Fiscal Year Final Research Report

• Project/Area Number: 20590594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2009-2012); Tokyo Metropolitan Institute of Gerontology (2008)
• Principal Investigator: TODA Tosifusa 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (80133635)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Magumi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究助手 (10159072) ; SHIBASAKI Futoshi 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (90300954)
• Project Period (FY): 2008 – 2012
• Keywords: 病態検査医学

Research Abstract

Proteomic analysis of oxidatively modified proteins was performed on spinal fluid of Alzheimer's disease patients. As a consequence of in-gel digestion and mass spectrometric identification, it has been clarified that transthyretin is preferentially oxidized in spinal fluid of Alzheimer's disease patients. Oxidative modification of transthyretin might be involved in incidence of Alzheimer's disease.

Research Products

• [Journal Article] Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats. (2012)
  • Author(s): Okita N, Hayashida Y, Kojima Y, Fukushima M, Yuguchi K, Mikami K, Yamauchi A, Watanabe K, Noguchi M, Nakamura M, Toda T, Higami Y.
  • Journal Title: Mech Ageing Dev. Volume: 133(5) Pages: 255-266
  • DOI: doi:10.1016/j.mad.2012.02.003
  • Peer Reviewed
• [Journal Article] Proteomic approaches to oxidative protein modifications implicated in the mechanism of aging (2012)
  • Author(s): Toda T, Nakamura M, Morisawa H, Hirota M, Nishigaki R, Yoshimi Y.
  • Journal Title: Geriatr Gerontol Int Volume: 10(Suppl.1) Pages: S25-S31
• [Journal Article] Up-regulation of 42 kDa tubulin alpha-6 chain fragment in well-differentiated hepatocellular carcinoma tissues from patients infected with hepatitis C virus (2011)
  • Author(s): Kuramitsu Y, Takashima M, Yokoyama Y, Iizuka N, Tamesa T, Akada JK, Wang Y, Toda T, Sakaida I, Okita K, Oka M, Nakamura K.
  • Journal Title: Anticancer Res. Volume: 31(10) Pages: 3331-3336
  • Peer Reviewed
• [Journal Article] Morphological changes in diabetic kidney are associated with increased O-GlcNAcylation of cytoskeletal proteins including alpha-actinin 4 (2011)
  • Author(s): Akimoto Y, Miura Y, Toda T, Wolfert MA, Wells L, Boons G-J, Hart GW, Endo T, Kawakami H
  • Journal Title: Clin Proteomics. Volume: 8(15) Pages: 1-16
  • DOI: doi:10.1186/1559-0275-8-15
  • Peer Reviewed
• [Journal Article] Quantitative evaluation of lectin-reactive glycoforms of alpha1-acid glycoprotein using lectin affinity capillary electrophoresis with fluorescence detection (2011)
  • Author(s): Shimura K, Tamura M, Toda T, Yazawa S, Kassai K
  • Journal Title: Electrophoresis Volume: 32(16) Pages: 2188-2193
  • DOI: doi:10.1002/elps.201100146
  • Peer Reviewed
• [Journal Article] Proteomic analysis of two types of exosomes in human whole saliva (2011)
  • Author(s): Ogawa Y, Miura Y, Harazono A, Kanai-Azuma M, Akimoto Y, Kawakami H, Yamaguchi T, Toda T, Endo T, Tsubuki M., Yanoshita R.
  • Journal Title: Biol. Pharm. Bull. Volume: 34(1) Pages: 13-23
  • Peer Reviewed
• [Journal Article] proteomic identification of differentially expressed genes in neural stem cells and neurons differentiated from embryonic stem cells of cynomolgus monkey (Macaca fascicularis) in vitro (2011)
  • Author(s): Akama K, Horikoshi T, Nakayama T, Otsu M, Imaizumi N, Nakamura M, Toda T, Inuma M, Hirano H, Kondo Y, Suzuki Y, Inoue N.
  • Journal Title: Biochim Biophys Acta. Volume: 1814 Pages: 265-276
  • DOI: doi:10.1016/j.bbapap.2010.10.009
  • Peer Reviewed
• [Journal Article] Proteomic analysis of plasma proteins in Japanese semisuper centenarians (2011)
  • Author(s): Miura Y, Sato Y, Arai Y, Abe Y, Takayama M, Toda T, Hirose N, Endo T.
  • Journal Title: Exp Gerontol. Volume: 46 Pages: 81-85
  • DOI: doi:10.1016/j.exger.2010.10.002
  • Peer Reviewed
• [Journal Article] Protein disulfide isomerase-P5, down-regulated in the final stage of boar epididymal sperm maturation, catalyzes disulfide formation to inhibit protein function in oxidative refolding of reduced denatured lysozyme. (2010)
  • Author(s): Akama K, Horikoshi T, Sugiyama A, Nakahata S, Akitsu A, Niwa N, Intoh A, Kakui Y, Sugaya M, Takei K, Imaizumi N, Sato T, Matsumoto R, Iwahashi H, Kashiwabara SI, Baba T, Nakamura M, Toda T.
  • Journal Title: Biochim Biophys Acta. Volume: 1804(6) Pages: 1272-1284
  • DOI: doi:10.1016/j.bbapap.2010.02.004
  • Peer Reviewed
• [Journal Article] Proteomic analysis of protein complexes in human SH-SY5Y neuroblastoma cells by using blue-native gel electrophoresis : An increase in lamin A/C associated with heat shock protein 90 in response to 6-hydroxydopamine-induced oxidative stress (2009)
  • Author(s): Nakamura M, Morisawa H, Imajoh-Ohmi S, Takamura C, Fukuda H, Toda T.
  • Journal Title: Exp. Gerontol. Volume: 44(6-7) Pages: 375-382
  • URL: http://dx.doi.org/10.1016/j.exger.2009.02.009
  • Peer Reviewed
• [Journal Article] Glycoproteomic analysis of abnormal N-glycosylation on the kappa chain of cryocryst alglobulin in a patient of multiple myeloma (2009)
  • Author(s): Toda T, Nakamura M, Yamada M, Nishine T, Torii T, Ikenaka K, Mori M.
  • Journal Title: J. Electrophoresis Volume: 53 Pages: 1-6
  • URL: http://dx.doi.org/10.2198/jelectroph.53.7
  • Peer Reviewed
• [Presentation] Proteomic identification of differentially expressed genes during differentiation of cynomolgus monkey embryonic stem cells to astrocyte progenitor cells in vitro (2012)
  • Author(s): Kuniko Akama1, Tomoe Horikoshi, Takashi Nakayama, Masahiro Otsu, Noriaki Imaizumi, Megumi Nakamura, Tosifusa Toda, Michiko Inuma, Hisashi Hirano, Yasushi Kondo, Yutaka Suzuki, Nobuo Inoue
  • Organizer: HUPO 11th Annual World Congress
  • Place of Presentation: ボストン、米国
  • Year and Date: 20120909-13
• [Presentation] 質量分析データリポジトリの開発 (2012)
  • Author(s): 森 澤拓、廣田三佳子、岩本真知子、三浦ゆり、戸田年総
  • Organizer: 第10回JHUPO日本プロテオーム学会
  • Place of Presentation: 東京
  • Year and Date: 20120726-27
• [Presentation] 二次元電気泳動分離スポットの質量分析による酸化メチオニンレベルの定量～タンパク質酸化修飾指標としての有用性について～ (2011)
  • Author(s): 戸田年総、岩本真知子、森澤拓、中家修一、尾島典行
  • Organizer: 第62回日本電気泳動学会
  • Place of Presentation: 横浜
  • Year and Date: 20111112-13
• [Presentation] メチオニンスルホキシドペプチドを標的としたフォーカストプロテオミクスによる細胞内酸化ストレス動態の網羅的解析 (2011)
  • Author(s): 戸田年総、岩本真知子、森澤拓、中家修一、尾島典行
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 20110921-24
• [Presentation] プロテオミクス用研究情報管理システムにおける電気泳動画像データ、質量分析データの表示、再解析機能の開発 (2011)
  • Author(s): 森澤 拓、廣田三佳子、岩本真知子、戸田年総
  • Organizer: 日本ヒトプロテオーム機構第9回大会(日本プロテオーム学会2011年会)
  • Place of Presentation: 新潟
  • Year and Date: 20110728-29
• [Presentation] 日本人超百寿者血漿タンパク質のプロテオミクス (2011)
  • Author(s): 三浦ゆり、新井康通、戸田年総、広瀬 信義、遠藤 玉夫
  • Organizer: 日本ヒトプロテオーム機構第9回大会(日本プロテオーム学会2011年会)
  • Place of Presentation: 新潟
  • Year and Date: 20110728-29
• [Presentation] プロテオーム解析による健康長寿マーカーの探索---日本人超百寿者血漿の網羅的解析--- (2011)
  • Author(s): 三浦ゆり、新井康通、戸田年総、広瀬信義、遠藤玉夫
  • Organizer: 日本基礎老化学会第34回大会
  • Place of Presentation: 東京
  • Year and Date: 20110615-17
• [Presentation] 脳脊髄液タンパク質の酸化還元状態の多角的プロテオーム解析 (2010)
  • Author(s): 戸田年総、岩本真知子、森澤 拓、吉澤利弘、芝崎 太
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会連合大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] 酸化ストレスによるラミンのリン酸化と分子シャペロン複合体形成のプロテオーム解析 (2010)
  • Author(s): 戸田年総、中村 愛
  • Organizer: 日本電気泳動学会第62回総会
  • Place of Presentation: 札幌
  • Year and Date: 20100918-19
• [Presentation] Neural stem sphere法によるサルの初期神経発生のプロテオーム解析 (2010)
  • Author(s): 赤間邦子、堀越朋恵、中山 孝、大津昌弘、今泉紀明、中村 愛、戸田年総、近藤 靖、鈴木 豊、井上順雄
  • Organizer: 第53回日本神経化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20100902-04
• [Presentation] Neural StemSphere法を用いたサルES細胞から神経幹細胞への分化過程における発現量変化解析 (2009)
  • Author(s): 今泉紀明, 堀越朋恵, 中山孝, 大津昌弘,赤間邦子, 中村愛, 戸田年総, 近藤靖, 鈴木豊, 井上順雄
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-24
• [Presentation] Proteome Analysis of Carbonyl Proteins in Cerebrospinal Fluid by Cy5-Hydrazide Labeling (2009)
  • Author(s): Tosifusa Toda, Megumi Nakamura, Futoshi shibasaki, Toshihiro Yoshizawa
  • Organizer: HUPO 8th Annual World Congress
  • Place of Presentation: Tronto、Canada
  • Year and Date: 20090926-30
• [Presentation] 酸化ストレス負荷におけるSH-SY5Y細胞のブルーネイティブ二次元電気泳動によるプロテオーム解析(II) (2009)
  • Author(s): 中村愛, 森澤拓, 戸田年総
  • Organizer: 日本ヒトプロテオーム機構第7回大会
  • Place of Presentation: 東京
  • Year and Date: 20090727-28
• [Presentation] 質量分析データビュワーの改良--プロテオーム研究情報管理のために-- (2009)
  • Author(s): 森澤拓, 中村愛, 廣田三佳子, 戸田年総
  • Organizer: 日本ヒトプロテオーム機構第7回会
  • Place of Presentation: 東京
  • Year and Date: 20090727-28