The role of GAPDH nitration in insulin signaling

• Project/Area Number: 15K01728
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: BABA Takeshi 順天堂大学, 医学部, 准教授 (80366450)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 心筋 / インスリン / 翻訳後修飾 / 2型糖尿病

Outline of Final Research Achievements

GAPDH is a catalytic enzyme commonly known to be involved in glycolysis. Increase in GAPDH nitration as well as phosphorylation was observed after insulin stimulation in the H9c2 cell line derived from embryonic rat ventricle. After glucose intraperitoneal injection, the phosphorylation and nitration levels of GAPDH were weak in cardiac muscle of type 2 diabetic rat compared with normal rat. These results demonstrated the possibility that insulin signaling mediated by GAPDH was impaired in the heart of type 2 diabetic rat. GAPDH was nitrated on Trp 311 after insulin stimulation of the H9c2 cell line. We mutated Trp 311 of GAPDH to Phe to prove that the nitration of Trp 311 acts as a trigger for the phosphorylation of GAPDH. The phosphorylation of the W/F GAPDH mutant diminished considerably compared to that of wildtype GAPDH after insulin stimulation in H9c2 cell line. These data suggest that the nitration of GAPDH may play a role in the insulin signal transduction in cardiac muscle.

Research Products

• [Journal Article] Accumulation of immunoglobulin G against Dermatophagoides farinae tropomyosin in dorsal root ganglia of NC/Nga mice with atopic dermatitis-like symptoms. (2017)
  • Author(s): Otsu A, Kawasaki H, Tominaga M, Shigenaga A, Matsuda H, Takahashi N, Nakajima T, Naito H, Baba T, Ogawa H, Tomooka Y, Yamakura F, Takamori K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 485 Issue: 4 Pages: 707-712
  • DOI: 10.1016/j.bbrc.2017.02.109
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of physical exercise on the nitrotryptophan-containing proteins in the rat hippocampus (2016)
  • Author(s): Uda M, Kawasaki H, Baba T, Shigenaga A, Yoshioka T, Yamakura F
  • Journal Title: Journal of Aomori Society of Sports Medicine Volume: 15 Pages: 7-13
  • Peer Reviewed / Open Access
• [Journal Article] Sumoylated α-skeletal muscle actin in the skeletal muscle of adult rats. (2015)
  • Author(s): Munehiro Uda、Hiroaki Kawasaki、Kyoichi Iizumi、Ayako Shigenaga、Takeshi Baba、Hisashi Naito、Toshitada Yoshioka 、Fumiyuki Yamakura
  • Journal Title: Molecular and Cellular Biochemistry Volume: 409 Issue: 1-2 Pages: 59-66
  • DOI: 10.1007/s11010-015-2512-1
  • Peer Reviewed / Open Access
• [Presentation] 6-ニトロトリプトファン-イムノクロマト法による検出の試み- (2017)
  • Author(s): 川崎広明、飯泉恭一、重永綾子、馬場猛、酒居一雄、後藤英樹、村井弘道、多々納俊雄、髙森建二、山倉文幸
  • Organizer: 第38回日本トリプトファン研究会学術集会
• [Presentation] Localization of IgG against D. farina-tropomyosin in dorsal root ganglia of NC/Nga mice with atopic dermatitis-like symptoms (2016)
  • Author(s): Otsu A, Kawasaki H, Tominaga M, Shigenaga A, Iizumi K, Baba T, Naito H, Ogawa H, Nakajima T, Tomooka Y, Yamakura F, Takamori K
  • Organizer: The 41st Annual Meeting of The Japanese Society for Investigative Dermatology
  • Place of Presentation: Sendai International Center
  • Year and Date: 2016-12-09
• [Presentation] 骨格筋で新たに見出された分子量の異なるα-アクチンの細胞内局在の検討 (2015)
  • Author(s): 宇田 宗弘、川崎 広明、飯泉 恭一、重永 綾子、馬場 猛、内藤久士、吉岡 利忠、山倉 文幸
  • Organizer: 第70回日本体力医学会大会
  • Place of Presentation: 和歌山県民文化会館
  • Year and Date: 2015-09-18