Physiological role of dietary nitrite

• Project/Area Number: 15H02898
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Eating habits
• Research Institution: The University of Tokushima
• Principal Investigator: TAMAKI Toshiaki 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (80179879)
• Co-Investigator(Kenkyū-buntansha): 井本 逸勢 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (30258610) ; 石澤 有紀 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (40610192) ; 池田 康将 徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (60432754) ; 土屋 浩一郎 徳島大学, 大学院医歯薬学研究部(薬学系), 教授 (70301314) ; 木平 孝高 徳島大学, 大学院医歯薬学研究部, 助教 (90377276)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 亜硝酸 / 硝酸 / エピゲノム / グルカゴン / AMP kinase / エピゲノム修飾 / AMPK / エピゲノム解析 / 栄養学 / 薬理学 / ケルセチン

Outline of Final Research Achievements

Impaired glucose tolerance occurs in high-fat diet loaded rats, but impaired glucose tolerance improves by simultaneously administering nitrite. This phenomenon suggested that direct activation of AMPK by nitrite and the inhibitory action on glucagon secretion may be involved.
Nitrite inhibited expression of endothelial injury marker VCAM-1 in human vascular endothelial cells and activated endothelial protective molecule ERK5. Long-term administration of nitrite to fatty toxicity was performed and DNA methylation analysis was performed. There was no significant difference in DNA methylation pattern with or without nitrite.

Research Products

• [Journal Article] Mechanisms of the pH- and Oxygen-Dependent Oxidation Activities of Artesunate (2018)
  • Author(s): Tsuda K, Miyamoto L, Hamano S, Morimoto Y, Kangawa Y, Fukue C, Kagawa Y, Horinouchi Y, Xu W, Ikeda Y, Tamaki T, Tsuchiya K
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 41 Issue: 4 Pages: 555-563
  • DOI: 10.1248/bpb.b17-00855
  • NAID: 130006602520
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide association study identifies ERBB4 on 2q34 as a novel locus associated with sperm motility in Japanese men (2018)
  • Author(s): Sato Y, Tajima A, Sato T, Nozawa S, Yoshiike M, Imoto I, Yamauchi A, Iwamoto T
  • Journal Title: J Med Genet Volume: - Issue: 6 Pages: 415-21
  • DOI: 10.1136/jmedgenet-2017-104991
  • Peer Reviewed / Open Access
• [Journal Article] Nitrite Activates 5′AMP-Activated Protein Kinase-Endothelial Nitric Oxide Synthase Pathway in Human Glomerular Endothelial Cells (2017)
  • Author(s): Miyamoto Licht、Yamane Megumi、Tomida Yosuke、Kono Mai、Yamaoka Tomomi、Kawasaki Aya、Hatano Aya、Tsuda Katsunori、Xu Wenting、Ikeda Yasumasa、Tamaki Toshiaki、Tsuchiya Koichiro
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 11 Pages: 1866-1872
  • DOI: 10.1248/bpb.b17-00316
  • NAID: 130006191905
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model. (2017)
  • Author(s): Yutaka Fukunaga, Yuki Izawa-Ishizawa, Yuya Horinouchi, Eriko Sairyo, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Yoshiro Abe, Ichiro Hashimoto, Toshiaki Tamaki.
  • Journal Title: Wound Repair and Regeneration Volume: 印刷中 Issue: 2 Pages: 217-223
  • DOI: 10.1111/wrr.12510
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A novel COL11A1 missense mutation in siblings with non-ocular Stickler syndrome (2016)
  • Author(s): Kohmoto T, Tsuji A, Morita K, Naruto T, Masuda K, Kashimada K, Enomoto K, Morio T, Harada H, Imoto I
  • Journal Title: Hum Genome Var Volume: 3 Issue: 1 Pages: 16003-16003
  • DOI: 10.1038/hgv.2016.3
  • Peer Reviewed / Open Access
• [Journal Article] Calcium signaling pathway is associated with the long-term clinical response to selective serotonin reuptake inhibitors (SSRI) and SSRI with antipsychotics in patients with obsessive-compulsive disorder. (2016)
  • Author(s): Umehara H, Numata S, Tajima A, Nishi A, Nakataki M, Imoto I, Sumitani S, Ohmori T.
  • Journal Title: PLoS One Volume: 11 Issue: 6 Pages: e0157232-e0157232
  • DOI: 10.1371/journal.pone.0157232
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Iron-induced skeletal muscle atrophy involves an Akt-forkhead box O3-E3 ubiquitin ligase-dependent pathway. (2016)
  • Author(s): Yasumasa Ikeda, Mizuki Imao, Akiho Satoh, Hiroaki Watanabe, Hirofumi Hamano, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Journal Title: Journal of Trace Elements in Medicine and Biology Volume: 35 Pages: 66-76
  • DOI: 10.1016/j.jtemb.2016.01.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice (2015)
  • Author(s): Soichiro Tajima, Yasumasa Ikeda, Hideaki Enomoto, Imao Mizuki, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Rihito Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki
  • Journal Title: European Journal of Nutrition Volume: 印刷中 Issue: 5 Pages: 709-719
  • DOI: 10.1007/s00394-014-0749-1
  • NAID: 120006732013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway. (2015)
  • Author(s): Ikeda Y, Hamano H, Satoh A, Horinouchi Y, Izawa-Ishizawa Y, Kihira Y, Ishizawa K, Aihara K, Tsuchiya K, Tamaki T
  • Journal Title: Hypertens Res. Volume: 38 Issue: 1 Pages: 733-740
  • DOI: 10.1038/hr.2015.118
  • NAID: 120006763917
  • Peer Reviewed
• [Journal Article] No association between the COMT Val158Met polymorphism and the long-term clinical response in obsessive-compulsive disorder in the Japanese population. (2015)
  • Author(s): Umehara H, Numata S*, Tajima A, Kinoshita M, Nakaaki S, Imoto I, Sumitani S, Ohmori T.
  • Journal Title: Hum Psychopharmacol. Volume: 30 Issue: 5 Pages: 372-376
  • DOI: 10.1002/hup.2485
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 身体運動時に生じる骨格筋代謝状態の変化における、中枢性調節機構の意義 (2017)
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  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール（長崎県、長崎市）
  • Year and Date: 2017-03-15
• [Presentation] Indoxyl Sulfate Involves Abnormality of Iron Metabolism Through Hepcidin Regulation (2017)
  • Author(s): Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Organizer: Experimental Biology 2017
  • Int'l Joint Research
• [Presentation] 食餌性亜硝酸塩の新たな薬理学的作用 (2017)
  • Author(s): 土屋浩一郎
  • Organizer: 第17回日本NO学会学術集会
• [Presentation] 食餌性硝酸・亜硝酸塩の生理的役割について (2017)
  • Author(s): 土屋浩一郎
  • Organizer: 第５３回全肥商連全国研修会
  • Invited
• [Presentation] 亜硝酸塩による空腹時血糖値改善の機序の解明 (2017)
  • Author(s): 服部真奈、宮本理人、山根萌、富田洋輔、土屋浩一郎
  • Organizer: 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
• [Presentation] Actinomyces spp.による硝酸イオンの還元と生理作用の検討 (2017)
  • Author(s): 別所将弘、村上主史、藤猪英樹、津田勝範、宮本理人、土屋浩一郎、池田康将、玉置俊晃、演野修一
  • Organizer: 2017年徳島県臨床検査技師会
• [Presentation] Long interspersed nuclear element-1 (LINE1)-mediated 8q13 microdeletion detected in a Japanese case with mesomelia-synostoses syndrome. (2016)
  • Author(s): Imoto I, Naruto T, Kohmoto T, Watanabe M, Ujiro S, Masuda K.
  • Organizer: The 66th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Vancouver Convention Centre (Vancouver, Canada)
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Nitrite activates 5’AMP-Activated Protein Kinase ; endothelial nitric oxide synthase pathway in human glomerular endothelial cells (2016)
  • Author(s): Koichiro Tsuchiya, Licht Miyamoto, Yosuke Tomida, Megumi Yamane, Yuuki Tsuchihashi, Katsunori Tsuda, Yasumasa Ikeda, Toshiaki Tamaki
  • Organizer: 第16回日本NO学会学術集会＆第９回国際NO学会
  • Place of Presentation: 仙台国際センター（宮城県、仙台市）
  • Year and Date: 2016-05-20
  • Int'l Joint Research
• [Presentation] ケルセチン代謝物Q3GAによる血管内皮細胞保護効果の検討 (2016)
  • Author(s): 斎藤尚子、石澤有紀、細岡真由子、木平孝高、今西正樹、座間味義人、池田康将、石澤啓介、土屋浩一郎、玉置俊晃
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2016-03-09
• [Presentation] ケルセチン代謝産物Q3GAの血管内皮膚細胞に対する短期及び長期効果の検討 (2016)
  • Author(s): 石澤 有紀, 細岡 真由子, 斎藤 尚子, 堀ノ内 裕也, 今西 正樹, 座間味 義人, 池田 康将, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃
  • Organizer: 第129回日本薬理学会近畿部会
  • Place of Presentation: 広島県医師会館（広島県、広島市）
• [Presentation] がん体細胞変異検出の特性からみた検査の考え方 (2016)
  • Author(s): 井本逸勢
  • Organizer: 第23回日本遺伝子診療学会大会
  • Place of Presentation: イイノホール＆カンファレンスセンター（東京都）
• [Presentation] Dietary nitrite and renal function (2016)
  • Author(s): Koichiro Tsuchiya
  • Organizer: Dongguk Universityの招待講演
  • Place of Presentation: College of Pharmacy, Dongguk University, Korea
  • Invited
• [Presentation] Quercetin による血管内皮細胞保護効果の検討 (2016)
  • Author(s): 細岡 真由子, 石澤 有紀, 斎藤 尚子, 今西 正樹, 座間味 義人, 宮本 理人, 堀ノ内 裕也, 池田 康将, 石澤 啓介, 玉置俊晃, 土屋 浩一郎
  • Organizer: 第130回日本薬理学会近畿部会
  • Place of Presentation: 京都大学百周年時計台記念館（京都府、京都市）
• [Presentation] Dietary nitrite ameliorates glucose tolerance and hyperlipidemia in diet-induced obesity rats. (2015)
  • Author(s): Yuki Tsuchihashi, Licht Miyamoto, Yosuke Tomida, Megumi Yamane, Kazuya Takenokuma, Yasumasa Ikeda, Toshiaki Tamaki, Koichiro Tsuchiya
  • Organizer: The 6th International Conference on Food Factors: ICoFF 2015
  • Place of Presentation: Coex, Seoul
  • Year and Date: 2015-11-22
• [Presentation] Limonenediol Ameliorates Lipid Profiles by Upregulation of Sirt1 Activity and Expression in Cultured Cells and High Fat Diet-Fed Mice. (2015)
  • Author(s): Licht Miyamoto, Haruna Aihara, Wenting Xu, Jin Meina, Yosuke Tomida, Tomomi Yamaoka, Naonobu Tanaka, Yasumasa Ikeda, Akira Shigenaga, Akira Otaka, Toshiaki Tamaki, Yoshiki Kashiwada, Koichiro Tsuchiya.
  • Organizer: 75th Scientific Sessions American Diabetes Association
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-06-05
• [Remarks] 德島大学医学部薬理学分野
  • URL: http://www.tuyakuri.umin.jp/