Search for Novel Functionalities of Amino Acids as Bio-regulatory Factors and Verification of Their Usefulness

• Project/Area Number: 20248014
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Niigata University
• Principal Investigator: KADOWAKI Motoni 新潟大学, 自然科学系, 教授 (90126029)
• Co-Investigator(Kenkyū-buntansha): KATO Hisanori 東京大学, 総括プロジェクト機構, 特任教授 (40211164) ; YOSHIZAWA Fumiaki 宇都宮大学, 農学部, 教授 (10269243) ; ODA Hiroaki 名古屋大学, 生命農学研究科, 准教授 (20204208) ; FURUYA Shigeki 九州大学, 農学研究院, 教授 (00222274) ; FUJIMURA Shinobu 新潟大学, 自然科学系, 准教授 (20282999)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥47,580,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥10,980,000); Fiscal Year 2010: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2009: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2008: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
• Keywords: アミノ酸 / マイクロアレイ / 発現制御 / 栄養学 / シグナル伝達 / マクロアレイ

Research Abstract

Collaborative works on the signal transduction and cell response to amino acids were undertaken mainly by using DNA microarray analysis. Thus, functionalities of amino acids, not as nutrients, but as signaling molecules, were analyzed regarding the regulation of protein synthesis and degradation, i. e., gene expression and autophagy, the regulations of carbohydrate metabolism and lipid metabolism, and a signaling mechanism of serine availability in the neuronal tissues. Complex information network structures of a variety of amino acids were partially clarified.

Research Products

• [Journal Article] Mild caloric restriction up-regulates the expression of prohibitin : A proteome study (2011)
  • Author(s): Takahashi, S., Masuda, J., Shimagami, H., Ohta, Y., Kanda, T., Saito, K. and Kato, H
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 405 Pages: 462-467
  • Peer Reviewed
• [Journal Article] The fat and protein fractions of freshwater clam(Corbicula fluminea) extract reduce serum cholesterol, and enhance bile acid biosynthesis and sterol excretion in hypercholesterolaemic rats fed a high-cholesterol diet (2011)
  • Author(s): Chijimatsu, T., Umeki, M., Okuda, Y., Yamada, K., Oda, H. and Mochizuki, S
  • Journal Title: Brit. J. Nutr Volume: 105 Pages: 526-534
  • Peer Reviewed
• [Journal Article] Regulation of muscular glutamate metabolism by high-protein diet in broiler chicks (2011)
  • Author(s): Kobayashi, H., Eguchi, A., Takano, W., Shibata, M., Kadowaki, M., and Fujimura, S
  • Journal Title: Anim. Sci. J. Volume: 82 Pages: 86-92
  • NAID: 10030375472
  • Peer Reviewed
• [Journal Article] Role of the renin-angiotensin-aldosterone system in the enhancement of salt sensitivity caused by prenatal protein restriction in stroke-prone spontaneously hypertensive rats (2011)
  • Author(s): Otani, L., Sugimoto, N., Kaji, M., Murai, M., Chang, S.-J., Kato, H. and Murakami, T
  • Journal Title: J. Nutr. Biochem Volume: (in press)
  • Peer Reviewed
• [Journal Article] An Optimized Method for the Determination of Free L-Cysteine in Rat Plasmaby High-Performance Liquid Chromatography Using the Derivatization Reagent 4-Aminosulfonyl-7-Fluoro-2, 1, 3-Benzoxadiazole (2011)
  • Author(s): Otani, L., Ogawa, S., Zhao, Z., Nakazawa, K., Umehara, S., Yoshimura, E., Chang, S.-J. andKato, H
  • Journal Title: Biosci. Biotechnol. Biochem Volume: (in press)
  • Peer Reviewed
• [Journal Article] Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-II-E cells (2010)
  • Author(s): Karim, MR., Fujimura, S., and Kadowaki, M
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 394 Pages: 981-987
  • Peer Reviewed
• [Journal Article] Improvement in the In Vivo Digestibility of Rice Protein by Alkali Extraction is Due to Structural Changes in Prolamin/Protein Body-Iparticle (2010)
  • Author(s): Kubota, M., Saito, Y., Masumura, T., Kumagai, T., Watanabe, R., Fujimura, S., and Kadowaki, M
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 74 Pages: 614-619
  • NAID: 10027553004
  • Peer Reviewed
• [Journal Article] Dietary protein deprivation up-regulatesinsulin signaling and in hibits gluconeogenesis in rat liver (2010)
  • Author(s): Toyoshima, Y, Tokita, R., Ohne, Y., Hakuno, F., Noguchi, T., Minami, S., Kato, H. and Takahashi, S. I
  • Journal Title: J. Mol. Endocrinol Volume: 45 Pages: 329-340
  • Peer Reviewed
• [Journal Article] Dietaryiron deficiency induces a variety of metabolic changes and even apoptosis in rat liver : a DNA microarray study (2010)
  • Author(s): Kamei, A., Watanabe, Y., Ishijima, T., Uehara, M., Arai, S., Kato, H., Nakai, Y. and Abe, K
  • Journal Title: Physiol. Genomics Volume: 42 Pages: 149-156
  • Peer Reviewed
• [Journal Article] 分枝鎖アミノ酸の代謝調節因子としての機能 (2010)
  • Author(s): 吉澤*史昭
  • Journal Title: 栄養生理研究会報 Volume: 54 Pages: 9-20
  • NAID: 10026688676
  • Peer Reviewed
• [Journal Article] Advantages of human hepatocyte-derivedtrans formants expressing a series of humancytochrome P-450 isoforms for genotoxicity examination (2010)
  • Author(s): Hashizume, T., Yoshitomi, S., Asahi, S., Uematsu, R., Matsumura, S., Chatani, F. and Oda, H
  • Journal Title: Toxicol. Sci Volume: 116 Pages: 488-497
  • Peer Reviewed
• [Journal Article] Brainspecific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine (2010)
  • Author(s): Yang, JH., Wada, A., Yoshida, K., Miyoshi, Y., Sayano, T., Esaki, K., Kinoshita, O. M., Tomonaga, S., Azuma, N., Watanabe, M., Hamase, K., Zaitsu, K., Machida, T., Messing, A., Itohara, S., Hirabayashi, Y., Furuya, S
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 41380-41390
  • Peer Reviewed
• [Journal Article] 遺伝性セリン合成不全疾患モデルマウスの脳内遊離アミノ酸組成に及ぼす大豆ペプチド摂取効果の定量的検討 (2010)
  • Author(s): 古屋茂樹
  • Journal Title: 大豆タンパク質研究 Volume: 13 Pages: 109-115
  • NAID: 40018765262
• [Journal Article] アミノ酸研究の最前線I (2010)
  • Author(s): 古屋茂樹
  • Journal Title: 外科と代謝・栄養 Volume: 44 Pages: 65-71
  • NAID: 10026098532
• [Journal Article] Improvement in the in Vivo Digestibility of Rice Protein by Alkali Extraction IsDue to Structural Changes in the Prolamin/Protein Body-I Particle. (2010)
  • Author(s): Kubota, M., et al.
  • Journal Title: Biosci Biotechnol Biochem. Volume: 74 Pages: 614-619
  • Peer Reviewed
• [Journal Article] Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-11-E cells. (2010)
  • Author(s): Karim, M.R., et al.
  • Journal Title: Biochem.Biophys.Res.Comm un. Volume: 394 Pages: 981-987
  • Peer Reviewed
• [Journal Article] Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis incontrolling the level of D-serine, an NMDA receptor co-agonist, in adult brain (2010)
  • Author(s): Yang, et al.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 41380-41390
  • Peer Reviewed
• [Journal Article] アミノ酸研究の最前線1 (2010)
  • Author(s): 古屋茂樹
  • Journal Title: 外科と代謝・栄養 Volume: 44 Pages: 65-71
• [Journal Article] Improvement in the in Vivo Digestibility of Rice Protein by Alkali Extraction Is Due to Structural Changes in the Prolamin/Protein Body-I Particle. (2010)
  • Author(s): Kubota, M., et al.
  • Journal Title: Biosci Biotechnol Biochem. 74 Pages: 614-619
  • Peer Reviewed
• [Journal Article] Vitamin E as a novel enhancer of macroautophagy in rat hepatocytes and H4-II-E cells. (2010)
  • Author(s): Karim, M.R., et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 394 Pages: 981-987
  • Peer Reviewed
• [Journal Article] Effect of mild restriction of food intake on gene expression profile in the liver of young rats : reference data for in vivo nutrigenomics study. (2010)
  • Author(s): Saito, K., et al.
  • Journal Title: Brit.J.Nutr. (印刷中)
  • Peer Reviewed
• [Journal Article] Effects of Rice Proteins from Two Cultivars, Koshihikari and Shunyo (2009)
  • Author(s): Yang, L., and Kadowaki, M. HepaticCholesterol Secretion by Isolated PerfusedLivers of Rats fed Cholesterol-Enriched Diets
  • Journal Title: Ann. Nutr. Metab. Volume: 54 Pages: 283-290
  • Peer Reviewed
• [Journal Article] Superiority of Alkali-Extracted Rice Proteinin Bioavailablity to Starch Degraded Rice Protein Comes from Digestion of Prolamin in Growing Rats (2009)
  • Author(s): Kumagai, T., Watanabe, R., Saito, M., Watanabe, T., Kubota, M., and Kadowaki, M
  • Journal Title: J. Nutr. Sci. Vitaminol. Volume: 55 Pages: 170-177
  • Peer Reviewed
• [Journal Article] Cytosolic LC3 ratio as a quantitative index of macroautophagy (2009)
  • Author(s): Kadowaki, M., Karim, MR
  • Journal Title: Methods in Enzymology Volume: Vol.452 Pages: 199-213
  • Peer Reviewed
• [Journal Article] A freshwater clam(Corbicula fluminea) extract reduces cholesterol level and hepatic lipids in normal rats and xenobioticsinduced hypercholesterolemic rats (2009)
  • Author(s): Chijimatsu, T., Tatsuguchi, I., Oda, H. andMochizuki, S
  • Journal Title: J. Agric. Food Chem. Volume: 57 Pages: 3108-3112
  • Peer Reviewed
• [Journal Article] In vitro micronucleus test in HepG2 transformants expressing a series of human cytochrome P450 isoforms with chemicals requiring metabolic activation (2009)
  • Author(s): Hashizume, T., Yoshitomi, S., Asahi, S., Matsumura, S., Chatani, F. and Oda, H
  • Journal Title: Mutation Res. Volume: 677 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Regular feeding plays an important role in cholesterol homeostasis through the liver circadian clock (2009)
  • Author(s): Yamajuku, D., Okubo, S., Haruma, T., Inagaki, T., Okuda, Y., Kojima T, Noutomi, K., Hashimoto, S. and Oda, H
  • Journal Title: Circulation Res. Volume: 105 Pages: 545-548
  • Peer Reviewed
• [Journal Article] Superiority of alkali-extracted rice protein in bioavailabilityce to starch degraded rice protein comes from digestion of prolamin in growing rats. (2009)
  • Author(s): Kumagai, T., et al.
  • Journal Title: J Nutr Sci Vitaminol. 55 Pages: 170-177
  • Peer Reviewed
• [Journal Article] Ethionine-induced ATP depletion represses mTOR signaling in the absence of increases in AMP-actiyated protein kinase activity in the rat liver. (2009)
  • Author(s): Yoshizawa F, et al.
  • Journal Title: Biosci Biotechnol Biochem. 73 Pages: 1984-1988
  • Peer Reviewed
• [Journal Article] Insulin mediates the linkage acceleration of muscle protein synthesis, thermogenesis, and heat storage by amino acids. (2009)
  • Author(s): Yamaoka I, et al.
  • Journal Title: Biochem Biophys Res Commun. 386 Pages: 252-256
  • Peer Reviewed
• [Journal Article] 生体調節因子として新たに注目される分岐鎖アミノ酸 (2009)
  • Author(s): 吉澤史昭
  • Journal Title: バイオサイエンスとインダストリー 67 Pages: 238-244
  • NAID: 10026194677
• [Journal Article] A freshwater clam(Corbicula fluminea)extract reduces cholesterol level and hepatic lipids in normal rats and xenobiotics-induced hypercholesterolemic rats. (2009)
  • Author(s): Chijimatsu, T., et al.
  • Journal Title: J.Agric.Food Chem. 57 Pages: 3108-3112
  • Peer Reviewed
• [Journal Article] In vitro micronucleus test in HepG2 transformants expressing a series of human cytochrome P450 isoforms with chemicals requiring metabolic activation. (2009)
  • Author(s): Hashizume, T., et al.
  • Journal Title: Mutation Res. 677 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Regular feeding plays an important role in cholesterol homeostasis through the liver circadian clock. (2009)
  • Author(s): Yamajuku, D., et al.
  • Journal Title: Circulation Res. 105 Pages: 545-548
  • Peer Reviewed
• [Journal Article] Impaired neurogenesis in the embryonic spinal cord of Phgdh knockout mouse, a serine deficiency disorder model. (2009)
  • Author(s): Kawakami Y., et al.
  • Journal Title: Neurosci.Res. 63 Pages: 184-193
  • Peer Reviewed
• [Journal Article] Superiority of Alkali-Extracted Rice Protein in Bioavailability to Starch Degraded Rice Protein Comes from Digestion of Prolamin in Growing Rats. (2009)
  • Author(s): Kumagai, T., Watanabe, R., Kadowaki, M., et al.
  • Journal Title: J. Nutr. Sci. Vitaminol. 55 Pages: 170-177
  • NAID: 10025970960
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes (2008)
  • Author(s): Klionsky, DL, Kadowaki, M.
  • Journal Title: Autophagy Volume: 4 Pages: 151-175
  • Peer Reviewed
• [Journal Article] Regulation of taste-active components of meatby dietary branched-chain amino acids : effects ofbranched-chain amino acid antagonism (2008)
  • Author(s): Kadowaki, M., Fujimura, S
  • Journal Title: Br. Poultry Sci. Volume: 49(3) Pages: 299-307
  • Peer Reviewed
• [Journal Article] Opposite effects of PU. 1 on mast cell stimulation. (2008)
  • Author(s): Niwa, Y., Nishiyama, C., Nakano, N., Kamei, A., Kato, H., 他
  • Journal Title: Biochem. Biophys. Res. Commun. 375 Pages: 95-100
  • Peer Reviewed
• [Presentation] マイクロアレイ解析から捉え直すセリン合成の栄養生理学的意義 (2010)
  • Author(s): 古屋茂樹
  • Organizer: 第4回日本アミノ酸学会学術集会ワークショップ
  • Place of Presentation: 第4回日本アミノ酸学会学術集会ワークショップ(日光市)
  • Year and Date: 2010-09-17
• [Presentation] セリン欠乏によって発現誘導される遺伝子の応答性は異なる (2010)
  • Author(s): 佐矢野智子
  • Organizer: 第4回日本アミノ酸学会学術集会
  • Place of Presentation: 第4回日本アミノ酸学会学術集会(日光市)
  • Year and Date: 2010-09-17
• [Presentation] Phgdh欠損線維芽細胞におけるオートファジー誘導と増殖抑制 (2010)
  • Author(s): 有本八潮
  • Organizer: 第4回日本アミノ酸学会学術集会
  • Place of Presentation: 第4回日本アミノ酸学会学術集会(日光市)
  • Year and Date: 2010-09-17
• [Presentation] アルギニンによるオートファジー調節機構はNO経路を介する (2010)
  • Author(s): 兼城賢二, 他
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島市
  • Year and Date: 2010-05-22
• [Presentation] Role of tocotrienol, vitamin E isomrs and their possible mechanism onautophagy regulation. (2010)
  • Author(s): Md.Razaul Karim, 他
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島市
  • Year and Date: 2010-05-22
• [Presentation] 脳内L-セリン合成能の低下は海馬NMDA受容体機能減弱を導く (2010)
  • Author(s): 和田晃
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島市
  • Year and Date: 2010-05-22
• [Presentation] タンパク質分解機構オートファジーの栄養制御学的研究 (2010)
  • Author(s): 門脇基二
  • Organizer: 第64回日本栄養・食糧学会大会
  • Place of Presentation: 徳島市(学会賞受賞講演)
  • Year and Date: 2010-05-21
• [Presentation] Isoleucine administration downregulates the genes for gluconeogenic rate-limiting enzymes (2010)
  • Author(s): Nodoka Oikawa
  • Organizer: Experimental Biology 2010
  • Place of Presentation: Anaheim ConventionCenter(USA)
  • Year and Date: 2010-04-28
• [Presentation] Functional study of an amino acid response element of the phosphoenolpyruvate carboxykinase 2(PEPCK2)gene. (2009)
  • Author(s): 石井駿介
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Cooking Makes Rice Prolamin Indigestible. (2009)
  • Author(s): Kubota M.
  • Organizer: 19th International Congress of Nutrition
  • Place of Presentation: タイ、バンコク
  • Year and Date: 2009-10-08
• [Presentation] イソロイシン経口投与によるラット肝臓での遺伝子発現変化の網羅的解析 (2009)
  • Author(s): 及川和
  • Organizer: 日本アミノ酸学会第3回学術大会
  • Place of Presentation: 京都
  • Year and Date: 2009-09-29
• [Presentation] 脳内セリン代謝とその機能 (2009)
  • Author(s): 古屋茂樹
  • Organizer: 第63回日本栄養・食糧学会大会 シンポジウム「アミノ酸の新しい機能とこれからの展開」
  • Place of Presentation: 長崎
  • Year and Date: 2009-05-22
• [Presentation] PEPCK2遺伝子のアミノ酸応答配列近傍領域の機能解析 (2008)
  • Author(s): 石井駿介, 加藤久典
  • Organizer: 第2回日本アミノ酸学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-02
• [Book] 網羅的遺伝子発現解析を利用した食品の安全性評価、「食の安全科学の展開-食のリスク予測と制御に向けて」(東京大学食の安全研究センター編) (2010)
  • Author(s): 加藤久典
  • Publisher: シーエムシー出版
• [Book] 食品データベース(第4章食品分野への応用)、「バイオチップ実用化ハンドブック」(金子周一、堀池靖浩編) (2010)
  • Author(s): 加藤久典、斉藤憲司
  • Publisher: エヌ・ティー・エス
• [Book] 窒素化合物の代謝「現代栄養学を理解するための分子生物学入門」 (2010)
  • Author(s): 加藤久典
  • Publisher: 光生館
• [Remarks] ニュートリゲノミクスデータベース
  • URL: http://nutrigenomics.jp/
• [Remarks] KEGGLEパスウェイ解析ツール
  • URL: http://keggle.jp/
• [Remarks] 第65回日本栄養・食糧学会大会イブニング・セミナー「栄養機能ゲノミクス研究会:DNAマイクロアレイをどのように使いこなすか?」を開催(2010年5月、徳島)