The role of GAPDH nitration in insulin signaling

2017 Fiscal Year Final Research Report

• 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
• Keywords: 心筋 / インスリン / 翻訳後修飾

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.

Free Research Field

生化学