The renal protective effects of nitrite salts in diabetic nephropathy model rats.

• Project/Area Number: 22590241
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: The University of Tokushima
• Principal Investigator: TSUCHIYA Koichiro 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (70301314)
• Co-Investigator(Kenkyū-buntansha): TOMITA Shuhei 鳥取大学, 医学部, 教授 (00263898) ; ISHIZAWA Keisuke 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (60398013) ; HAMANO Shuichi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60530392) ; TAMAKI Toshiaki 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (80179879)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腎臓 / 亜硝酸 / 亜硝酸塩 / 一酸化窒素 / 代謝 / 腎保護作用 / 耐糖能 / 硝酸塩 / 糸球体内皮細胞 / ラット / AMPK / STZ / MIN6細胞 / 硝酸 / 経口 / 腎糸球体内皮細胞 / マウス / OGTT

Research Abstract

Nitric oxide (NO) plays multipotent effects in many kinds of physiological processes. NO is generated by NO synthase (NOS), and disorders in the NOS is known to be related to diabetic nephropathy. Therefore, it has been believed that the production of NO from nitrite by non-enzymatic or enzymatic reduction responsible for the renoprotective effects of it. However, in this study, we found that nitrite suppress intracellular ATP level, then activates 5’AMP-activated protein kinase(AMPK), and following endotherial NOS activation. The activation of AMPK-eNOS pathway in endotherial cells is supposed to play a significant renal protective role in the nitrite action in addition to the NOS-independent NO production by nitrite.

Research Products

• [Journal Article] 亜硝酸塩による腎保護作用( (2013)
  • Author(s): 土屋浩一郎、石澤啓介、宮本理人、堀ノ内裕也、池田康将、木平孝高、冨田修平、玉置俊晃
  • Journal Title: 腎とフリーラジカル Volume: 11 Pages: 30-33
• [Journal Article] Significance of AMPK-eNOS pathway in renal protective effects of nitrite (2013)
  • Author(s): Tsuchiya K, Miyamoto L, Yamane M, Kono M, Tomida Y, Ishizawa K, Kihira Y, Ikeda Y, Tamaki T
  • Journal Title: Nitric Oxide Volume: S24 Pages: S24-S24
  • DOI: 10.1016/j.niox.2013.02.029
• [Journal Article] 亜硝酸塩による腎保護作用（総説） (2013)
  • Author(s): 土屋浩一郎
  • Journal Title: 腎とフリーラジカル Volume: 11 Pages: 30-33
• [Journal Article] Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular end otbelial cells (2011)
  • Author(s): Fukuhara Y
  • Journal Title: J.Med.Invest. Volume: 58 Pages: 118-126
  • Peer Reviewed
• [Journal Article] Dietary nitrite ameliorates renal injury in L-NAME-induced hypertensive rats (2010)
  • Author(s): Tsuchiya K, et al
  • Journal Title: Nitric Oxide Volume: 22 Pages: 98-103
  • Peer Reviewed
• [Presentation] 亜硝酸塩による腎保護作用とその機序 (2013)
  • Author(s): 土屋浩一郎、宮本理人、石澤啓介、冨田洋輔、山根萌、木平孝高、池田康将、玉置俊晃
  • Organizer: 第66回日本酸化ストレス学会
  • Place of Presentation: ウインク愛知(愛知県)
  • Year and Date: 2013-06-14
• [Presentation] 亜硝酸による腎保護作用における AMPK の意義 (2013)
  • Author(s): 宮本理人、山根萌、河野舞、冨田洋輔、石澤啓介、玉置俊晃、土屋浩一郎
  • Organizer: 第42回 日本心脈管作動物質学会
  • Place of Presentation: 奈良県新公会堂(奈良県)
  • Year and Date: 2013-02-09
• [Presentation] Significance of AMPK-eNOS pathway in renal protective effects of nitrite. Fifth International Meeting on the role of Nitrite and Nitrate in Pathology (2013)
  • Author(s): Tsuchiya K, Miyamoto L, Yamane M, Kono M, Tomida Y, Ishizawa K, Kihira Y, Tamaki T
  • Organizer: Pathophysiology, and Therapeutics
  • Place of Presentation: The University Club(USA)
• [Presentation] 亜硝酸塩における腎保護作用におけるAMPKの意義 (2013)
  • Author(s): 土屋浩一郎 他
  • Organizer: 第42回 日本心脈管差動物質学会
  • Place of Presentation: 奈良県新公会堂（奈良県）
• [Presentation] Significance of AMPK-eNOS pathway in renal protective effects of nitrite (2013)
  • Author(s): 土屋浩一郎 他
  • Organizer: Fifth International Meeting on the role of Nitrite and Nitrate in Pathology, Pathophysiology, and Therapeutics
  • Place of Presentation: The University Club（USA）
• [Presentation] 亜硝酸塩による腎保護作用とその機序 (2013)
  • Author(s): 土屋浩一郎 他
  • Organizer: 第66回日本酸化ストレス学会
  • Place of Presentation: ウインク愛知（愛知県）
• [Presentation] 亜硝酸塩による腎保護作用 (2011)
  • Author(s): 土屋浩一郎
  • Organizer: 第23回腎とフリーラジカル研究会
  • Place of Presentation: 徳島市(ホテルグランドパレス徳島)(招待講演)
  • Year and Date: 2011-10-02