Study on the disease induced by imbalance of tetrahydrobiopterin-metabolism and research on the mechanisms for protection against the state.

• Project/Area Number: 25460346
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Fujita Health University
• Principal Investigator: Sumi-Ichinose Chiho 藤田保健衛生大学, 医学部, 准教授 (10247653)
• Co-Investigator(Renkei-kenkyūsha): Kondo Kazunao 藤田保健衛生大学, 医学部, 教授 (90270983) ; Ichinose Hiroshi 東京工業大学, 大学院生命理工学研究科, 教授 (90192492)
• Research Collaborator: Ihira Noriko 藤田保健衛生大学, 医学部, 研究補助員
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2013: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: テトラヒドロビオプテリン / ドパミン / 一酸化窒素 / 高血圧 / 交感神経 / 持続勃起症 / 血管 / ドパミンニューロン / ドパミン神経

Outline of Final Research Achievements

We identified some candidate genes which are influenced by tetrahydrobiopterin (BH4) during early developmental stage after birth. Dihydrobiopterin (BH2) content in the plasma of Qdpr-/- mice much increased. However, BH2/BH4 ratio in the aorta of Qdpr-/- mice was only 1.6 times higher, for BH4 content in the aorta also increased. The aortic rings from Qdpr-/- mice were relaxed by acetylcholine as much as those from wild type ones. Spr-/-mice suffered from unstable hypertension and bradycardia, and male Spr-/- mice showed serious priapism at high incidence. Biopterin- and monoamine-content were remarkably reduced in the tissue. Aortic ring of Spr-/- mice was supersensitive to alpha1 agonist, and relaxation response to acetylcholine decreased.

Research Products

• [Journal Article] Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia (2014)
  • Author(s): Takanori Onouchi, Katsunori Kobayashi, Kazuyoshi Sakai, Atsushi Shimomura, Ron Smits, Chiho Sumi-Ichinose, Masafumi Kurosumi Keizo Takao, Ryuji Nomura, Akiko Iizuka-Kogo, Hidenori Suzuki,Kazunao Kondo, Tetsu Akiyama Tsuyoshi Miyakawa Riccardo Fodde and Takao Senda, Riccardo Fodde, Takao
  • Journal Title: Molecular Brain Volume: 7 Issue: 1 Pages: 21-21
  • DOI: 10.1186/1756-6606-7-21
  • Peer Reviewed / Open Access
• [Journal Article] Disturbed biopterin and folate metabolism in the Qdpr-deficient mouse. (2014)
  • Author(s): Xu F, Sudo Y, Sanechika S, Yamashita J, Shimaguchi S, Honda S, Sumi-Ichinose C, Mori-Kojima M, Nakata R, Furuta T, Sakurai M, Sugimoto M, Soga T, Kondo K, Ichinose H.
  • Journal Title: FEBS Letters Volume: 588 Issue: 21 Pages: 3924-3931
  • DOI: 10.1016/j.febslet.2014.09.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Sepiapterin reductase knockout mice suffered from unstable hypertension and serious priapism. (2016)
  • Author(s): ①Chiho Sumi-Ichinose, Yui Suganuma, Taiki Kano, Noriko Ihira, Kazuhisa Ikemoto, and Kazunao Kondo.
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2016-03-09
• [Presentation] Hypoxiaが血管内皮細胞における細胞内テトラヒドロビオプテリン量と細胞増殖に及ぼす影響 (2015)
  • Author(s): ②池本和久、菅沼由唯、狩野泰輝、野村隆英、一瀬千穂、近藤一直
  • Organizer: 第29回日本プテリジン研究会
  • Place of Presentation: 多摩 日本医科大学多摩永山病院会議室
  • Year and Date: 2015-11-21
• [Presentation] キノノイド型ジヒドロプテリン還元酵素遺伝子ノックアウトマウス大動脈リング標本の血管弛緩反応 (2015)
  • Author(s): ③一瀬―鷲見千穂、菅沼由唯、狩野泰輝、井平典子、池本和久、一瀬 宏、近藤一直
  • Organizer: 第29回日本プテリジン研究会
  • Place of Presentation: 多摩 日本医科大学多摩永山病院会議室
  • Year and Date: 2015-11-21
• [Presentation] Aortic relaxation by acethlcholine is maintained against hyper dihydrobiopterinemia in quinonoid-dihydrobiopterin reductase knockout mice (2015)
  • Author(s): Chiho Sumi-Ichinose, Yui Suganuma, Taiki Kano, Noriko Ihira, Kazuhisa Ikemoto, Takahide Nomura, and Kazunao Kondo
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: Naggoya, Japan
  • Year and Date: 2015-03-18 – 2015-03-20