Function and metabolism of a histidine-containing dipeptide, carnosine, in mammals

• Project/Area Number: 23570164
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: OKUMURA Nobuaki 大阪大学, たんぱく質研究所, 准教授 (20224173)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ペプチド代謝 / ジペプチダーゼ / 金属プロテアーゼ / 骨格筋 / 脳 / カルノシン / ジペプチド / ペプチダーゼ / アミノ酸代謝 / carnosine / dipeptidase / histidine / histamin / metallopeptidase

Research Abstract

Carnosine is a histidine-containing dipeptides present at high concentrations in mammalian skeletal muscles and the brain. It has been proposed that they have a variety of biological functions including anti-oxidant, pH-buffering and nutritional activities. Recently, we and other groups have identified the enzymes responsible for carnosine synthesis and degradation, but the function of these enzymes are still to be investigated. In this study, in order to clarify the functional roles of these enzymes, we have analyzed the enzymatic characteristics and cellular distribution of these enzymes, especially focusing on a carnosine-degrading enzyme, carnosine dipeptidase II (CN2).

Research Products

• [Journal Article] Diversity in protein profiles of individual calcium oxalate kidney stones (2013)
  • Author(s): Okumura N, Tsujihata M, Momohara C, Yoshioka I, Suto K, Nonomura N, Okuyama A, Takao T.
  • Journal Title: PLoS One Volume: 8 Pages: 68624-68624
• [Journal Article] Identification of cargo proteins specific for importin-beta with importin-alpha applying a stable isotope labeling by amino acids in cell culture (SILAC)-based in vitro transport system (2013)
  • Author(s): Kimura M, Okumura N, Kose S, Takao T, Imamoto N.
  • Journal Title: J. Biol. Chem. Volume: 288 Pages: 24540-24549
• [Journal Article] Identification of cargo proteins specific for the nucleocytoplasmic transport carrier transportin by combination of an in vitro transport system and stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics (2013)
  • Author(s): Kimura M, Kose S, Okumura N, Imai K, Furuta M, Sakiyama N, Tomii K, Horton P, Takao T, Imamoto N.
  • Journal Title: Mol Cell Proteomics Volume: 12 Pages: 145-157
• [Journal Article] Diversity in protein profiles of individual calcium oxalate kidney stones. (2013)
  • Author(s): Okumura N, Tsujihaga M, Yoshioka I, Suto K, Nonomura N, Okuyama A, Takao T
  • Journal Title: PlosOne Volume: 8 Issue: 7 Pages: e68624-e68624
  • DOI: 10.1371/journal.pone.0068624
  • Peer Reviewed
• [Journal Article] Identification of cargo proteins specific for importin-β with importin-α applying a stable isotope labeling by amino acids in cell culture (SILAC)-based in vitro transport system. (2013)
  • Author(s): Kimura M, Okumura N, Kose S, Takao T, Imamoto N,
  • Journal Title: J.Biol. Chem. Volume: 288 Issue: 34 Pages: 24540-24549
  • DOI: 10.1074/jbc.m113.489286
  • Peer Reviewed
• [Journal Article] Identification of cargo proteins specific for the nucleocytoplasmic transport carrier transportin by combination of an in vitro transport system and stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics. (2013)
  • Author(s): Kimura Makoto
  • Journal Title: Molecular & Cellular Proteomics Volume: 12 Issue: 1 Pages: 145-157
  • DOI: 10.1074/mcp.m112.019414
  • Peer Reviewed
• [Journal Article] Role of L-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats : involvement of the circadian clock and histamine (2012)
  • Author(s): Nagai K, Tanida M, Niijima A, Tsuruoka N, Kiso Y, Horii Y, Shen J, Okumura N.
  • Journal Title: Amino Acids Volume: 43 Pages: 97-109
• [Journal Article] Role of L-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine. (2012)
  • Author(s): Nagai K, Tanida M, Niijima A, Tsuruoka N, Kiso Y, Horii Y, Shen J, Okumura N.
  • Journal Title: Amino acids Volume: 43 Issue: 1 Pages: 97-109
  • DOI: 10.1007/s00726-012-1251-9
  • Peer Reviewed
• [Journal Article] Role of L: -carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine. (2012)
  • Author(s): Nagai K, Tanida M, Niijima A, Tsuruoka N, Kiso Y, Horii Y, Shen J, Okumura N.
  • Journal Title: Amino Acids Volume: 25
  • Peer Reviewed
• [Journal Article] Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation. (2011)
  • Author(s): Kim C, Aono S, Marubashi S, Wada H, Kobayashi S, Eguchi H, Takeda Y, Tanemura M, Okumura N, Takao T, Doki Y, Mori M, Nagano H.
  • Journal Title: Journal of Surgical Research Volume: Available on line on Mar 25
  • Peer Reviewed
• [Presentation] Requirement of dimer formation for carnosine-hydrolyzing activity of carnosinase CNDP2 (2011)
  • Author(s): Okumura N., Kusunoki, M., Okumura A., Nagai, K., Takao T.
  • Organizer: Poster presentation at International congress on carnosine in exercise and disease
  • Place of Presentation: Belgium
• [Presentation] ESI-TOF MSを用いたカルノシンジペプチダーゼ2 (CNDP2)のダイマー形成の解析 (2011)
  • Author(s): 田村淳, 高尾敏文, 奥村宣明
  • Organizer: 第59回質量分析討論会
  • Place of Presentation: 大阪
• [Presentation] Requirement of dimer formation for carnosine-hydrolyzing activity of CNDP2 (2011)
  • Author(s): Okumura N, Kusunoki M, Okumura A, Nagai K,Takao T
  • Organizer: International Congress in Carnosine in Health and Disease
  • Place of Presentation: ベルギー、ゲント
• [Presentation] ESI-TOF MS を用いたカルノシンジペプチダーゼ2 (CNDP2) のダイマー形成の解析 (2011)
  • Author(s): 奥村宣明、田村淳、高尾敏文
  • Organizer: 第59回質量分析討論会
  • Place of Presentation: 大阪
• [Book] Carnosine and the control of blood glucose (2015)
  • Author(s): Okumura N, Tanida T, Niijima A, Tsuruoka N, Kiso Y, Horii Y, Nagai K
  • Total Pages: 10
  • Publisher: Royal Soriety of Chemistry Publishing
• [Book] Handbook of Proteolytic Enzymes, 3rd edition (2013)
  • Author(s): Nobuaki Okumura （分担執筆、N.D.Rawlings, Guy Sulvesen編）
  • Publisher: Academic Press
• [Book] Carnosine dipeptidase II (in Handbook of Proteolytic Enzymes) (2012)
  • Author(s): Okumura N.
  • Publisher: Academic Press (Waltham, MA)
• [Book] 蛋白質実験ノート第4版 (2011)
  • Author(s): 奥村宣明 （分担執筆) （岡田雅人、三木裕明、宮崎香編）
  • Total Pages: 53
  • Publisher: 羊土社
• [Book] 生物学辞典 (2011)
  • Author(s): 奥村宣明 (分担執筆)
  • Publisher: 岩波書店
• [Book] Carnosine and the blood glucose. (in Food and Nutritional Components in Focus)
  • Author(s): Okumura N. Tanida M. Niijima A, Tsuruoka N. Kiso Y. Horii Y. Nagai K.
  • Publisher: RSC publishing (London)
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/metabolism/taisha.html
• [Remarks] 体内環境統合蛋白質研究グループ
  • URL: http://www.protein.osaka-u.ac.jp/metabolism/taisha.html