Analyses of molecular mechanisms of homeostasis by carnosine in mammals and carnosine-hydrolyzing enzyme, CNDP2

• Project/Area Number: 20570132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: OKUMURA Nobuaki Osaka University, 蛋白質研究所, 准教授 (20224173)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ペプチド / ペプチダーゼ / 立体構造 / ホメオスタシス / カルノシン / 代謝 / 視床下部 / 反応機構 / 自律神経

Research Abstract

Carnosine (beta-alanyl-L-histidine) is a dipeptide present at high concentrations in mammalian muscles and brain. Carnosine has been suggested to be ace as an antioxidant, but its function as well as the enzymes responsible for its synthesis and degradation has not well been understood. We have previously found an enzyme that can hydrolyze carnosine (CNDP2), and then in the present study, we have analyzed the structure, function and distrubution of CNDP2. We have determine the crystal structure of CNDP2 and revealed its structural features. In addition, we have found that it is highly expressed in the histaminergic neurons in the hypothalamus, raising a possibility that carnosine and CNDP2 may contribute the production of substrate for histamine synthesis.

Research Products

• [Journal Article] Nerve growth factor attenuates 2-deoxy-d-glucose-triggered endoplasmic reticulum stress-mediated apoptosis via enhanced expression of GRP78. (2010)
  • Author(s): Kishi S, Shimoke K, Nakatani Y, Shimada T, Okumura N, Nagai K, Shin-Ya K, Ikeuchi T.
  • Journal Title: Neurosci Res. 66 Pages: 14-21
• [Journal Article] PACAP-deficient mice exhibit light parameter-dependent abnormalities on nonvisual photoreception and early activity onset. (2010)
  • Author(s): Kawaguchi C, Isojima Y, Shintani N, Hatanaka M, Guo X, Okumura N, Nagai K, Hashimoto H, Baba A.
  • Journal Title: PLoS One. Feb18;5(2)
• [Journal Article] 尿のペプチドミクス (2010)
  • Author(s): 奥村宣明、須藤浩三、高尾敏文
  • Journal Title: 日本腎臓学会誌 52 Pages: 485-488
  • NAID: 10026409259
• [Journal Article] Coordinated regulation of circadian rhythms and homeostasis by the suprachiasmatic nucleus. (2010)
  • Author(s): Nakagawa H, Okumura N.
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci. 86 Pages: 391-409
  • NAID: 130000258736
• [Journal Article] 筋肉からの代謝・自律神経ネットワークを介した血圧調節 (2010)
  • Author(s): 永井克也、谷田守、新島旭、奥村宣明
  • Journal Title: 血圧 17 Pages: 854-859
• [Journal Article] PACAP-deficient mice exhibit light parameter-dependent abnormalities on nonvisual photoreception and early activity onset. (2010)
  • Author(s): Kawaguchi C.
  • Journal Title: PLoS One.Feb 18 ; 5(2) : e9286(2010) Volume: 5
  • Peer Reviewed
• [Journal Article] Coordinated regulation of circadian rhythms and homeostasis by the suprachiasmatic nucleus. (2010)
  • Author(s): Nakagawa H.
  • Journal Title: Proc.Jpn.Acad.Sci.Ser.B. Volume: 86 Pages: 391-409
  • Peer Reviewed
• [Journal Article] 尿のペプチドミクス (2010)
  • Author(s): 奥村宣明
  • Journal Title: 日本腎臓学会誌 Volume: 52 Pages: 485-488
  • NAID: 10026409259
• [Journal Article] 筋肉からの代謝、自律神経ネットワークを介した血圧調節 (2010)
  • Author(s): 永井克也
  • Journal Title: 血圧 Volume: 17 Pages: 854-859
• [Journal Article] PACAP-deficient mice exhibit light parameter-dependent abnormalities on nonvisual photoreception and early activity onset (2010)
  • Author(s): Chihiro Kawaguchi
  • Journal Title: PLoS One 18
  • Peer Reviewed
• [Journal Article] Nerve growth factor attenuates 2-deoxy-d-glucose-triggered endoplasmic reticulum stress-mediated apoptosis via enhanced expression of GRP78 (2010)
  • Author(s): Soichiro Kishi
  • Journal Title: Neurosci Res 66 Pages: 14-21
  • Peer Reviewed
• [Journal Article] 乳酸菌の腸内投与による自律神経活動と生理機能の変化 (2009)
  • Author(s): 永井克也、谷田守、福島洋一、山野俊彦、新島旭、前田景子、奥村宣明、堀井裕子、沈嬌
  • Journal Title: 腸内細菌学雑誌 23 Pages: 209-216
  • NAID: 10027119273
• [Journal Article] Structural basis for substrate recognition and hydrolysis by mouse carnosinase CN2. (2008)
  • Author(s): Unno, H., Yamashita, T., Ujita, S., Okumura N., Otani, H., Okumura, A., Nagai K., Kusunoki, M.
  • Journal Title: J Biol Chem 283 Pages: 27289-99
• [Journal Article] Colocalization of a carnosine-splitting enzyme, tissue carnosinase (CN2)/cytosolic non-specific dipeptidase 2 (CNDP2), with histidine decarboxylase in the tuberomammillary nucleus of the hypothalamus. (2008)
  • Author(s): Otani, H., Okumura, A., Nagai K., Okumura N.
  • Journal Title: Neurosci Lett 445 Pages: 166-9
• [Journal Article] Interaction of alpha1-syntrophin with multiple isoforms of heterotrimeric G protein alpha subunits. (2008)
  • Author(s): Okumura, A., Nagai K., Okumura N.
  • Journal Title: FEBS J 275 Pages: 22-33
• [Journal Article] Localization of phospho-tyrosine489-beta-adducin immunoreactivity in the hypothalamic tanycytes and its involvement in energy homeostasis. (2008)
  • Author(s): Gotoh, H., Okumura, A., Nagai K., Okumura N.
  • Journal Title: Brain Res 1228 Pages: 97-106
• [Journal Article] structural Basis for Substrate Recognition and Hydrolysis by Mouse Carnosinase CN2 (2008)
  • Author(s): Hideaki Unno
  • Journal Title: Journal of Biological Chemistry 283 Pages: 27289-27299
  • Peer Reviewed
• [Journal Article] Colocalization of a carnosine-splitting enzyme, tissuecarnosinase(CN2)/cytosolic non-specific dipeptidase 2 (CNDP2), with histidine decarboxylase in the tuberomammillary nucleus of the hypothalamus (2008)
  • Author(s): Hiroto Otani
  • Journal Title: Neuroscience Let ters 445 Pages: 166-169
  • Peer Reviewed
• [Journal Article] Interaction of alphal-syntrophin with multiple isoformsof heterotrimeric G protein alpha subunits (2008)
  • Author(s): Akiko Okumura
  • Journal Title: FEBS Journal 275 Pages: 22-33
  • Peer Reviewed
• [Journal Article] Localization of phospho-tyrosine489-β-adducin immunoreactivity in the hypothalamic tanycytes and its involvement in energy homeostasis (2008)
  • Author(s): Hitoshi Gotoh
  • Journal Title: Brain Research 1228 Pages: 97-106
  • Peer Reviewed
• [Presentation] カルノシンジペプチダーゼCNDP2の酵素反応におけるダイマー形成の役割 (2010)
  • Author(s): 奥村宣明
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸 ポートピアホテル、国際会議場
  • Year and Date: 2010-12-07
• [Presentation] Requirement of dimer formation for enzymatic reaction of mouse carnosine dipeptidase 2 (CNDP2) (2010)
  • Author(s): Okumura N, Kusunoki M, Takao T
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会合同大会
• [Presentation] バイオマーカー探索のための尿のペプチドミクス (2009)
  • Author(s): 奥村宣明、高尾敏文
  • 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: 2009-07-29
• [Presentation] Peptidomic analysis for biomarker discovery (2009)
  • Author(s): 奥村宣明
  • Organizer: 日本ヒトプロテオーム学会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-29
• [Presentation] Interaction of alphal-syntrophin with multiple isoformsof heterotrimeric G protein alpha subunits (2008)
  • Author(s): Nobuaki Okumura
  • Organizer: 日本生化学会大会・日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Remarks] ホームページ等
  • URL: http://www.protein.osaka-u.ac.jp/metabolism
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/metabolism/index.html
• [Remarks]
  • URL: http://www.protein.Osaka-u.ac.jp/metabolism/taisha.html