Clinical application and biochemical analysis of the citrullinated proteins which catalyzed by peptidylarginine deiminase

• Project/Area Number: 23590441
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: MARUYAMA Naoki 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, 研究部長 (00115940)
• Co-Investigator(Kenkyū-buntansha): KAGAMI Yayoi 地方独立行政法人東京都健康長寿医療センター, 研究所, 研究員 (80557661)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 酵素 / 蛋白質 / 癌 / シトルリン / PAD / シトルリン化 / 測定系

Research Abstract

We developed two novel methods for sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of human peptidylarginine deiminase 4 (hPAD4) and the detection of hPAD4 autoantibodies in the peripheral blood. The combination of these sandwich ELISA methods might be a potentially beneficial clinical tool for diagnosing RA.

Research Products

• [Journal Article] Peptidylarginine deiminase and protein citrullination in prion diseases (2013)
  • Author(s): Jang, B., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Journal Title: Strong evidence of neurodegeneration Volume: Prion 7 Pages: 42-46
• [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis (2013)
  • Author(s): Ishigami, A., Uchida, Y., Miyazaki, T., Handa, S., Choi, E.K,, Kim, Y.S,, Kasahara, Y., Maruyama, N.
  • Journal Title: Mod Rheumatol Volume: 23 Pages: 794-803
  • NAID: 10031189176
• [Journal Article] Peptidylarginine deiminase and protein citrullination in prion diseases: Strong evidence of neurodegeneration. (2013)
  • Author(s): Jang, B., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Journal Title: Prion Volume: 7 Issue: 1 Pages: 42-46
  • DOI: 10.4161/pri.22380
  • Peer Reviewed
• [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis. (2013)
  • Author(s): Ishigami, A., Uchida, Y., Miyazaki, T., Handa, S., Choi, E.K,, Kim, Y.S,, Kasahara, Y., Maruyama, N.
  • Journal Title: Mod Rheumatol. Volume: 23 Issue: 4 Pages: 794-803
  • DOI: 10.1007/s10165-012-0748-0
  • NAID: 10031189176
  • Peer Reviewed
• [Journal Article] Peptidylarginine deiminase modulates the physiological roles of enolase via citrullination : links between altered multifunction of enolase and neurodegenerative diseases (2012)
  • Author(s): Jang, B., Jeon, Y.C., Choi, J.K., Park, ., Kim, J.I., Ishigami, A., Maruyama, ., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Journal Title: Biochem. J Volume: 445 Pages: 183-192
• [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis. (2012)
  • Author(s): Ishigami, A., Uchida, Y., Miyazaki, T., Handa, S., Choi, E.K,, Kim, Y.S,, Kasahara, Y., Maruyama, N.
  • Journal Title: Mod Rheumatol Volume: in press
  • NAID: 10031189176
  • Peer Reviewed
• [Journal Article] Peptidylarginine deiminase modulates the physiological roles of enolase via citrullination: links between altered multifunction of enolase and neurodegenerative diseases. (2012)
  • Author(s): Jang, B., Jeon, Y.C., Choi, J.K., Park, M., Kim, J.I., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Journal Title: Biochem J Volume: 445 Pages: 183-192
  • Peer Reviewed
• [Journal Article] 3,4-diaminopyridine improves neuromuscular transmission in a MuSK antibodies-induced mouse model of myasthenia gravis. (2012)
  • Author(s): Mori, S., Kishi, M., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Konishi, T., Maruyama, N., Shigemoto, K.
  • Journal Title: J Neuroimmunol Volume: 245 Pages: 75-78
  • Peer Reviewed
• [Journal Article] Antibodies against Muscle-Specific Kinase Impair Both Presynaptic and Postsynaptic Functions in a Murine Model of Myasthenia Gravis. (2012)
  • Author(s): Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Hotta, H., Desaki, J., Kishi, M., Konishi, T., Nishino, Y., Miyazawa, A., Maruyama, N., Shigemoto, K.
  • Journal Title: Amr J Pathol Volume: 180 Pages: 798-810
  • Peer Reviewed
• [Journal Article] Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice : nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins (2011)
  • Author(s): Jang, B., Shin, HY., Choi, JK., Nguyen, du PT., Jeong, BH., Ishigami, A., Maruyama, N., Carp, RI., Kim, YS., and Choi, EK.
  • Journal Title: J. Neuropathol. Exp. Neurol Volume: 70 Pages: 116-124
• [Journal Article] Shimada, S., Tanaka, Y., Waki, H., Kon, K., Iwamoto, M., Maruyama, N.: Analysis of brain cell activation by nanosized particles of Ginkgo biloba extract. (2011)
  • Author(s): Shimada, S., Tanaka, Y., Waki, H., Kon, K., Iwamoto, M., Maruyama, N.
  • Journal Title: International Journal of Plant Physiology and Biochemistry Volume: 3 Pages: 28-33
  • Peer Reviewed
• [Journal Article] 17beta-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30. (2011)
  • Author(s): Fukui, M., Senmaru, T., Hasegawa, G., Yamazaki, M., Asano, M., Kagami, Y., Ishigami, A., Maruyama, N., Iwasa, K., Kitawaki, J., Itoh, Y., Okanoue, T., Ohta, M., Obayashi, H., Nakamura, N.
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Pages: 252-257
  • Peer Reviewed
• [Journal Article] Absorption and excretion of ascorbic acid alone and in acerola (Malpighia emarginata) juice: comparison in healthy Japanese subjects. (2011)
  • Author(s): Uchida, E., Kondo, Y., Amano, A., Aizawa, S., Hanamura, T., Aoki, H., Nagamine, K., Koizumi, T., Maruyama, N., Ishigami, A.
  • Journal Title: Biol Pharm Bull Volume: 34 Pages: 1744-1747
  • NAID: 130001252859
  • Peer Reviewed
• [Journal Article] Establishment and characterization of hepatocytes from an Immortomouse/SMP30/GNL knockout mouse hybrid lacking vitamin C to study vitamin C transport. (2011)
  • Author(s): Amano, A., Handa, S., Aigaki, T., Shigemoto, K., Maruyama, N., Ishigami, A.
  • Journal Title: J Biochem Volume: 150 Pages: 671-678
  • NAID: 10030589294
  • Peer Reviewed
• [Journal Article] Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice. J Physiol Sci 61: 201-209 (2011) (2011)
  • Author(s): Hotta, H., Uchida, S., Kagitani, F., Maruyama, N.
  • Journal Title: J Physiol Sci Volume: 61 Pages: 201-209
  • Peer Reviewed
• [Journal Article] Mitochondrial reactive oxygen species generation by the SDHC V69E mutation causes low birth weight and neonatal growth retardation. (2011)
  • Author(s): Ishii, T., Miyazawa, M., Onodera, A., Yasuda, K., Kawabe, N., Kirinashizawa, M., Yoshimura, S., Maruyama, N., Hartman, P.S., Ishii, N.
  • Journal Title: Mitochondrion Volume: 11 Pages: 155-165
  • Peer Reviewed
• [Journal Article] Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice: nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins. (2011)
  • Author(s): Jang, B., Shin, H.Y., Choi, J.K., Nguyen du, P.T., Jeong, B.H., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Journal Title: J Neuropathol Exp Neurol Volume: 70 Pages: 116-124
  • Peer Reviewed
• [Journal Article] Time course of vitamin C distribution and absorption after oral administration in SMP30/GNL knockout mice. (2011)
  • Author(s): Iwama, M., Shimokado, K., Maruyama, N., Ishigami, A.
  • Journal Title: Nutrition Volume: 27 Pages: 471-478
  • NAID: 110008762053
  • Peer Reviewed
• [Journal Article] 基礎老化学による老年歯科医学への貢献. (2011)
  • Author(s): 丸山直記、石神昭人
  • Journal Title: 老年歯科医学 Volume: 26 Pages: 286-290
  • NAID: 10031137163
• [Journal Article] SMP30/GNLノックアウトマウスを用いた経口摂取によるビタミンCの血液、尿、組織への移行速度および移行量の解析. (2011)
  • Author(s): 岩間水輝、下門顕太郎、丸山直記、石神昭人
  • Journal Title: ビタミン Volume: 85 Pages: 601-603
• [Journal Article] 加齢による臓器障害. (2011)
  • Author(s): 加賀美弥生, 丸山直記
  • Journal Title: 生体の科学 Volume: 62 Pages: 257-261
• [Presentation] Age-related changes of peptidylarginine deiminase 2 in the mouse brain (2013)
  • Author(s): Kagami, Y., Shimada, N., Handa, S., Choi, E.K., Kim, Y.S., Ito, H., Maruyama, N., Ishigami, A.
  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics (IAGG 2013)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2013-06-26
• [Presentation] Peptidylarginine deiminase 2-mediat ed protein citrullinati on in prion disease (2013)
  • Author(s): Kim, H.J., Jang, B., Jin, J.K., Jeon, Y.C., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics (IAGG 2013)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2013-06-26
• [Presentation] hPAD4測定及びhPAD4自己抗体検出による関節リウマチの臨床診断 (2013)
  • Author(s): 丸山直記, 石神昭人
  • Organizer: 第57回日本老年医学会関東甲信越地方会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-23
• [Presentation] hPAD4測定及びhPAD4自己抗体検出による関節リウマチ臨床診断薬の開発 (2013)
  • Author(s): 石神昭人, 半田節子, 加賀美弥生, 内田好昭, 丸山直記
  • Organizer: 第133回日本薬学会
  • Place of Presentation: 横浜
• [Presentation] Age-related changes of peptidylarginine deiminase 2 in the mouse brain. (2013)
  • Author(s): Kagami, Y., Shimada, N., Handa, S., Choi, E.K., Kim, Y.S., Ito, H., Maruyama, N., Ishigami, A.
  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics (IAGG 2013)
  • Place of Presentation: Seoul, Korea
• [Presentation] Peptidylarginine deiminase 2-mediat ed protein citrullinati on in prion disease. (2013)
  • Author(s): Kim, H.J., Jang, B., Jin, J.K., Jeon, Y.C., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics (IAGG 2013)
  • Place of Presentation: Seoul, Korea
• [Presentation] 腫瘍組織におけるシトルリン化タンパク質の局在と病態との相関 (2012)
  • Author(s): 加賀美弥生, 半田節子, 根本哲生, 丸山直記, 石神昭人
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] 関節リウマチの早期診断を目指した新規hPAD4測定法及びhPAD4自己抗体検出法の確立 (2012)
  • Author(s): 半田節子, 加賀美弥生, 内田好昭, 笠原靖, 丸山直記, 石神昭人
  • Organizer: 第85回日本生化学大会
  • Place of Presentation: 福岡
• [Presentation] ビタミンCの欠乏がマウス皮膚に及ぼす影響 (2012)
  • Author(s): 佐藤安訓, 新井浩司, 西山敏夫, 野村義宏, 岸本祐樹, 相澤真悟, 丸山直記, 石神昭人
  • Organizer: 日本ビタミン学会第64回大会
  • Place of Presentation: 岐阜
• [Presentation] SMP30&SOD1ダブルノックアウトマウスの病理学的解析 (2011)
  • Author(s): 岩間水輝, 野田義博, 清水孝彦, 丸山直記, 石神昭人
  • Organizer: 第33回日本基礎老化学会シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2011-10-08
• [Presentation] ヒトでの1回摂取によるビタミンCの血中移行, 尿中排泄の検討 (2011)
  • Author(s): 石神昭人, 相澤真悟, 千田美紀, 相垣敏郎, 丸山直記, 千田俊哉
  • Organizer: 第135回ビタミンC研究委員会
  • Place of Presentation: 島根
  • Year and Date: 2011-09-02
• [Presentation] ビタミンC欠乏がカテコールアミン生合成系に及ぼす影響 (2011)
  • Author(s): 天野晶子, 角田誠, 相垣敏郎, 丸山直記, 石神昭人
  • Organizer: 日本ビタミン学会第63回大会
  • Place of Presentation: 広島
• [Presentation] ヒトSMP30のX線結晶構造解析 (2011)
  • Author(s): 相澤真悟, 千田美紀, 相垣敏郎, 丸山直記, 石神昭人, 千田俊哉
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: 大阪
• [Presentation] SMP30/GNLノックアウトマウスを用いたカテコールアミン生合成系に及ぼすビタミンC欠乏の影響 (2011)
  • Author(s): 天野晶子,角田誠,相垣敏郎,丸山直記,石神昭人
  • Organizer: 第34回日本基礎老化学会大会
  • Place of Presentation: 東京
• [Presentation] 老化・老年学による他研究領域への貢献 (2011)
  • Author(s): 丸山直記, 石神昭人
  • Organizer: 第9回次世代を担う若手のためのフィジカル・ファーマフォーラム(PPF)2011
  • Place of Presentation: 箱根
• [Presentation] マウス卵巣におけるSMP30の発現と調節機構 (2011)
  • Author(s): 加賀美弥生, 石神昭人, 丸山直記
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ヒト及びマウスSMP30/GNLのX線結晶構造解析とデヒドロアスコルビン酸分解活性 (2011)
  • Author(s): 相澤真悟, 千田美紀, 相垣敏郎, 丸山直記, 千田俊哉, 石神昭人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ビタミンC合成不全SMP30/GNL遺伝子破壊マウスを用いた妊娠, 出産時のビタミンC不足が新生児に与える影響 (2011)
  • Author(s): 岸本祐樹, 金井孝夫, 下門健太郎, 丸山直記, 石神昭人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Evaluation of antioxidant activity of Olive Oil Potato Chips after oral administration in vitamin C-deficient SMP30/GNL knockout mice. (2011)
  • Author(s): Sakuma,R., Kondo, Y., Ichisawa, M., Ishihara, K., Kubo, M., Ohashi, M., Handa, S., Mugita, H., Maruyama, N., Koga, H., Ishigami, A.
  • Organizer: International Society for Nutraceuticals and Functional Foods (ISNFF)
  • Place of Presentation: Sapporo
• [Presentation] Effect of vitamin C deficiency on noradrenaline synthesis. (2011)
  • Author(s): Amano, A., Tsunoda, M., Aigaki, T., Maruyama, N., Ishigami, A.
  • Organizer: The 9th Asia/Oceania Regional Congress of Gerontology
  • Place of Presentation: Melbourne, Australia,
• [Presentation] ビタミンC欠乏マウスにおける活性酸素種は増加する. (2011)
  • Author(s): 近藤嘉高、加賀美弥生、半田節子、石神昭人、丸山直記
  • Organizer: 第65回日本栄養・食糧学会
  • Place of Presentation: 東京
• [Presentation] Smp30/Sod1ダブルノックアウトマウスにおける肝臓の組織学的解析 (2011)
  • Author(s): 岩間水輝、野田義博、清水孝彦、近藤嘉高、丸山直記、石神昭人
  • Organizer: 日本ビタミン学会第63回大会,
  • Place of Presentation: 広島
• [Presentation] SMP30/GNLノックアウトマウスを用いたカテコールアミン生合成系に及ぼすビタミンC欠乏の影響. (2011)
  • Author(s): 天野晶子, 角田誠, 相垣敏郎, 丸山直記, 石神昭人
  • Organizer: 第34回日本基礎老化学会大会
  • Place of Presentation: 東京
• [Presentation] ヒトでの１回摂取によるビタミンCの血中移行、尿中排泄の検討. (2011)
  • Author(s): 石神昭人、相澤真悟、千田美紀、相垣敏郎、丸山直記、千田俊哉
  • Organizer: 第135回ビタミンC研究委員会
  • Place of Presentation: 島根
• [Presentation] 老化・老年学による他研究領域への貢献 (2011)
  • Author(s): 丸山直記、石神昭人
  • Organizer: 第9回次世代を担う若手のためのフィジカル・ファーマフォーラム(PPF)2011(招待講演)
  • Place of Presentation: 箱根
• [Presentation] ヒト及びマウスSMP30/GNLのX線結晶構造解析とデヒドロアスコルビン酸分解活性. (2011)
  • Author(s): 相澤真悟、千田美紀、相垣敏郎、丸山直記、千田俊哉、石神昭人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 基礎老化学による老年歯科医学への貢献 (2011)
  • Author(s): 丸山直記
  • Organizer: 日本老年歯科医学会 第２２回学術大会(招待講演)
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.aging-regulation.jp/