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      Nature Communications published Prof. KONG Lingyi team's research results of 4-OI anti-inflammatory mechanism

      Release date:2019-11-14  Release:主页英文版


      November 8th, the internationally renowned academic journal Nature Communications (IF:11.878) published the latest research results of the team of Professor KONG Lingyi from CPU School of Chinese Medicine, "4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects". Doctoral candidate LIAO Shanting and Associate Professor HAN Chao are co-first authors, Professor KONG Lingyi and Professor WANG Junsong are the co-corresponding authors. China Pharmaceutical University is the first author instituion and the first communication unit.


      In the host of the National Natural Science Foundation's key project "Integrated PK/PD and Metabolomics of Huanglian Jiedu Decoction in the basic research of pharmacodynamics," the authors found that the energy metabolism of septic rats changed from oxidative phosphorylation to aerobic sugar. Fermentation confirms that aerobic glycolysis plays an important role in the development of inflammation. 4-octyl itaconic acid (4-OI) is a derivative of the small molecule metabolite itaconic acid, having the structure of an α,β-unsaturated ketone, which can alkylate the sulfhydryl group on the protein. The results of protein mass spectrometry showed that 4-OI directly acts on the 22nd position of the cysteine residue on GAPDH, and inhibited its enzyme activity and reduced the release of inflammatory factors. Metabolic flow experiments showed that 4-OI blocked glycolysis at GAPDH, decreased extracellular acidification rate, and increased intracellular oxygen consumption. Further BMDM cells knocked out by Irg1 showed reduced endogenous itaconic acid production, which increased the rate of glycolysis and the release of disease factors. In animal models, it was further confirmed that 4-OI is effective in inhibiting inflammation. This study provides novel insights into the regulation of 4-OI-mediated metabolic reprogramming and highlights the importance of targeting aerobic glycolysis in the treatment of inflammatory diseases, which provides new ideas for the development of new anti-inflammatory drugs in the future.


      Article link: https://www.nature.com/articles/s41467-019-13078-5


      Written by LIAO Shanting

      Translated by LIU Qi



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