Mechanism of food rejection upon amino acid-unbalanced diet

• Project/Area Number: 16K15194
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: ISHII Isao 昭和薬科大学, 薬学部, 教授 (90292953)
• Research Collaborator: KAMATA Shotaro
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 摂食拒絶 / 必須アミノ酸 / 非必須アミノ酸 / 拒食症 / 摂食 / アミノ酸 / 遺伝子改変マウス / 行動学 / 栄養学 / 生理学 / 神経科学

Outline of Final Research Achievements

We investigated the physiological correlation between food rejection behavior and serum amino acid (AA) profiles upon single AA-deficient diets in mice. When fed an essential AA-deprived diet, we observed decreased serum levels of the corresponding AA followed by food rejection (although the time of onset differs among the diets). Meanwhile, when fed a non-essential AA-deprived diet, both food rejection and its preceding serum AA level change were not observed. Furthermore, when fed a non-essential cyst(e)ine-deprived diet, normal (wild-type) mice did not show food rejection as well as serum Cys level decrease; however, genetically-engineered mice deficient in Cys biosynthesis (cystathionine gamma-lyase [CSE]-knockout mice) did show those. There results suggest that food rejection upon AA deprivation from diet could occur when serum levels of any proteinogenic AA are declined.

Research Products

• [Int'l Joint Research] kyungpook National University/Keimyung University(韓国)
• [Int'l Joint Research] Friedrich-Alexander University/Charity Campus Virchow/Erlangen University(ドイツ)
• [Int'l Joint Research] University of Exeter(英国)
• [Int'l Joint Research] Universite Paris Descartes(フランス)
• [Int'l Joint Research] Washington State University/University of Michigan, Ann Arbor(米国)
• [Int'l Joint Research] Kyungpook National University/Korea Institute of Radiol and Med Sci(韓国)
• [Int'l Joint Research]
• [Journal Article] Hydrogen sulfide inhibits the NLRP3 inflammasome and reduces cytokine production both in vitro and in a mouse model of inflammation (2018)
  • Author(s): Castelblanco M, Lugrin J, Ehirchiou D, Nasi S, Ishii I, So A, Martinon F, Busso N
  • Journal Title: J Biol Chem Volume: 293 Issue: 7 Pages: 2546-2557
  • DOI: 10.1074/jbc.m117.806869
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• [Journal Article] Structural and functional insights into S-thiolation of human serum albumins. (2018)
  • Author(s): Nakashima F, Shibata T, Kamiya K, Yoshitake J, Kikuchi R, Matsushita T, Ishii I, Gimenez-Bastida JA, Schneider C, Uchida K
  • Journal Title: Sci Rep. Volume: 8(1) Issue: 1 Pages: 932-932
  • DOI: 10.1038/s41598-018-19610-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Capture of Cadmium by Reactive Polysulfides Attenuates Cadmium-Induced Adaptive Responses and Hepatotoxicity (2017)
  • Author(s): Akiyama Masahiro、Shinkai Yasuhiro、Unoki Takamitsu、Shim Ilseob、Ishii Isao、Kumagai Yoshito
  • Journal Title: Chem Res Toxicol Volume: 30 Issue: 12 Pages: 2209-2217
  • DOI: 10.1021/acs.chemrestox.7b00278
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• [Journal Article] Hydrogen sulfide-producing cystathionine γ-lyase is critical in the progression of kidney fibrosis (2017)
  • Author(s): Han Sang Jun、Noh Mi Ra、Jung Jung-Min、Ishii Isao、Yoo Jeongsoo、Kim Jee In、Park Kwon Moo
  • Journal Title: Free Radic Biol Med Volume: 112 Pages: 423-432
  • DOI: 10.1016/j.freeradbiomed.2017.08.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rapid 2D DIGE Proteomic Analysis of Mouse Liver (2017)
  • Author(s): Kamata Shotaro、Ishii Isao
  • Journal Title: Methods Mol Biol Volume: 1664 Pages: 153-166
  • DOI: 10.1007/978-1-4939-7268-5_13
  • ISBN: 9781493972678, 9781493972685
  • Peer Reviewed
• [Journal Article] Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion. (2017)
  • Author(s): Takahashi N, Wei FY, Watanabe S, Hirayama M, Ohuchi Y, Fujimura A, Kaitsuka T, Ishii I, Sawa T, Nakayama H, Akaike T, Tomizawa K.
  • Journal Title: Nucleic Acids Res. Volume: 45 Issue: 1 Pages: 435-445
  • DOI: 10.1093/nar/gkw745
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2016)
  • Author(s): Klionsky DJ., Abdelmohsen K., Abe A., Abedin MJ.,Inomata M., et al.
  • Journal Title: Autophagy Volume: 12(1) Issue: 1 Pages: 1-222
  • DOI: 10.1080/15548627.2015.1100356
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation. (2016)
  • Author(s): Wedmann R, Onderka C, Wei S, Szijarto IA, Miljkovic JL, Mitrovic A, Lange M, Savitsky S, Yadav PK, Torregrossa R, Harrer EG, Harrer T, Ishii I, Gollasch M, Wood ME, Galardon E, Xian M, Whiteman M, Banerjee R, Filipovic MR.
  • Journal Title: Chemical Science Volume: 7 Issue: 5 Pages: 3414-3426
  • DOI: 10.1039/c5sc04818d
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Blockade of Sphingosine 1-Phosphate Receptor 2 Signaling Attenuates High-Fat Diet-Induced Adipocyte Hypertrophy and Systemic Glucose Intolerance in Mice (2016)
  • Author(s): Kitada Y, Kajita K, Taguchi K, Mori I, Yamauchi M, Ikeda T, Kawashima M, Asano M, Kajita T, Ishizuka T, Banno Y, Kojima I, Chun J, Kamata S, Ishii I, Morita H.
  • Journal Title: Endocrinology Volume: 印刷中 Issue: 5 Pages: 1839-1851
  • DOI: 10.1210/en.2015-1768
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of cystathionine gamma-lyase in immediate renal impairment and inflammatory response in acute ischemic kidney injury. (2016)
  • Author(s): Marko L, Szijarto IA, Filipovic MR, Kassmann M, Balogh A, Park JK, Przybyl L, N'Diaye G, Kramer S, Anders J, Ishii I, Muller DN, Gollasch M.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27517-27517
  • DOI: 10.1038/srep27517
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immobilization of the gas signaling molecule H2S by radioisotopes: detection, quantification, and in vivo imaging. (2016)
  • Author(s): Sarkar S, Ha YS, Soni N, An GI, Lee W, Kim MH, Huynh PT, Ahn H, Bhatt N, Lee YJ, Kim JY, Park KM, Ishii I, Kang SG, Yoo J.
  • Journal Title: Angewandte Chemie (International ed. in English) Volume: 55 Issue: 32 Pages: 9365-9370
  • DOI: 10.1002/anie.201603813
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cystathionine-gamma-lyase gene deletion protects mice against inflammation and liver sieve injury following polymicrobial sepsis. (2016)
  • Author(s): Gaddam RR, Fraser R, Badiei A, Chambers S, Cogger VC, Le Couteur DG, Ishii I, Bhatia M.
  • Journal Title: PLoS One Volume: 11 Issue: 8 Pages: e0160521-e0160521
  • DOI: 10.1371/journal.pone.0160521
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 二系統の高ホモシステイン血症マウスにおける脳脊髄液アミノ酸組成異常 (2018)
  • Author(s): 横山 輝, 赤星 軌征，石井 功
  • Organizer: 日本薬学会年会
• [Presentation] Cystathionine gamma－lyase欠損母マウスにおける授乳行動異常 (2018)
  • Author(s): 赤星 軌征，半田 博紀，横山 輝，石井 功
  • Organizer: 日本薬学会年会
• [Presentation] Cystathionine gamma-lyase欠損マウスにおける妊娠高血圧症候群と育児放棄 (2017)
  • Author(s): 赤星 軌征，半田 博紀，石井 功
  • Organizer: フォーラム2017
• [Presentation] Cystathionine gamma-lyase欠損マウスにおける乳清アミノ酸成分の異常 (2017)
  • Author(s): 半田 博紀，横山 輝, 赤星 軌征，石井 功
  • Organizer: フォーラム2017
• [Presentation] Novel targets of homocysteine, a risk factor for cardiovascular disease (2017)
  • Author(s): Isao Ishii
  • Organizer: 韓国薬学会秋季国際学会
  • Int'l Joint Research / Invited
• [Presentation] 新電子物質からの生体防御におけるトランススルフレーション酵素(CBS/CTH)の役割 (2016)
  • Author(s): 石井 功
  • Organizer: フォーラム2017衛生薬学・環境トキシコロジー
  • Place of Presentation: 昭和大学（東京都 品川区）
  • Invited
• [Presentation] Possible roles of H2S/RSS and homocysteine in the redox signaling via electrophiles. (2016)
  • Author(s): Ishii I
  • Organizer: The 9th International Conference on the Biology, Chemistry, and Therapeutic applications of NO.
  • Place of Presentation: 仙台国際センタ－（宮城県 仙台市）
  • Int'l Joint Research / Invited
• [Presentation] Dietary deprivation of each proteinogenic amino acid induces altered systemic responses in mice. (2016)
  • Author(s): Kamata S, Yamamoto J, Kamijo K, Ochiai T, Morita T, Yoshitomi Y, Hagia Y, Kubota M, Ohkubo R, Karube K, Kasahara T, Ishii I.
  • Organizer: The 9th International Conference on the Biology, Chemistry, and Therapeutic applications of NO.
  • Place of Presentation: 仙台国際センタ－（宮城県 仙台市）
  • Int'l Joint Research
• [Presentation] Dietary deprivation of each proteinogenic amino acid induces differential systemic responsess in mice. (2016)
  • Author(s): Kamata S, Yamamoto J, Karube K, Ohkubo R, Kasahara T, Ishii I.
  • Organizer: Experimental Biology 2016
  • Place of Presentation: San Diego (USA)
  • Int'l Joint Research
• [Book] 第６版 衛生薬学 ー健康と環境ー (2018)
  • Author(s): 石井 功
  • Total Pages: 538
  • Publisher: 丸善出版株式会社
  • ISBN: 9784621301784