The role of nitric oxide derived from xanthine oxidoreductase in renal vascular system

• Project/Area Number: 26461232
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyushu University
• Principal Investigator: Ohtsubo Toshio 九州大学, 医学研究院, 准教授 (30423974)
• Research Collaborator: HAGA Yoshie ; MURAKAMI Noboru ; KANSUI Yasuo ; GOTO Kenichi ; MATSUMURA Kiyoshi ; NOGUCHI Hideko
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 虚血再灌流障害 / 活性酸素 / キサンチンオキシドリダクターゼ / 血管 / キサンチン酸化還元酵素 / 一酸化窒素 / キサンチン産生酵素 / 虚血再灌流 / キサンチンオキシダーゼ / 亜硝酸

Outline of Final Research Achievements

Study using XOR gene disrupted mice. 1) Renal ischemia reperfusion induced severe renal damage in XOR+/+ mice compared to XOR+/- mice. ROS generated by XOR increased the expression of inflammation related genes and induced the damage to the cortical region in kidney. 2) Administration of nitrite before ischemia protected renal tissue from ischemia reperfusion injury. 3) Hypoxia/reoxygenation induced the expression of XOR mRNA in human endothelial cells. 4) Administration of LNAME increased the systolic blood pressure in XOR+/- mice compared to XOR+/+ mice and induced vascular dilatation and degeneration of the media at thoracic aorta wall in XOR+/- mice. 5) The deletion of both XOR and eNOS gene showed significant decrease in life span.

Research Products

• [Presentation] 腎虚血再灌流障害におけるXanthine Oxidoreductaseの役割 (2015)
  • Author(s): 6.芳賀祥江、大坪俊夫、関拓紀、寒水康雄、後藤健一、松村潔、北園孝成
  • Organizer: 38回日本高血圧学会総会
  • Place of Presentation: 松山
  • Year and Date: 2015-10-09
• [Presentation] 腎虚血再灌流障害におけるXanthine Oxidoreductaseの２つの働き (2015)
  • Author(s): 芳賀祥江、大坪俊夫、土橋卓也
  • Organizer: 第48回日本痛風・核酸代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-19 – 2015-02-20
• [Presentation] Disruption of xanthine oxidoreductase gene attenuates renal ischemia-reperfusion injury in mice. (2014)
  • Author(s): Yoshie Haga, Toshio Ohtsubo, Noboru Murakami, Yasuo Kansui, Kenichi Goto, Takunori Seki, Kiyoshi Matsumura and Takanari Kitazono
  • Organizer: The 25nd Scientific Meeting of the international Society of Hypertension.
  • Place of Presentation: Athens, Greece
  • Year and Date: 2014-06-13 – 2014-06-16