A new pathological mechanism of glioma centered in hypotaurine was disclosed through functional metabolomics research by groups 1808, 18M0 and 1106 of DICP in collaborative study with NIH of US and The first affiliated Hospital of Haerbin Medical University. By using capillary electrophoresis – mass spectrometry, researchers found that hypotaurine was elevated in glioma tissues compared to that in the paracancerous tissues. Furthermore, tissue hypotaurine content was closely correlated with tumor grade. Through molecular docking analysis, researchers found that hypotaurine could competitively bind to PHD2 as compared withα-ketoglutarate. This binding resulted in enzymatic activity inhibition. Under normoxia, PHD2 can hydroxylate hypoxia inducible factor- 1α(HIF-1α) and lead to the degradation of HIF-1α. Inhibition of PHD2 causes its inability to hydroxylate HIF-1αeven under normoxia. The intact HIF-1αbinds to its ß subunit and forms a functionally competent diamer and enters into the nucleus to trigger many oncogenes expression. Hypotaurine’s inhibition effects were confirmed in vivo and in vitro at molecular and cellular levels. Additionally, glioma cells ingesting the oxidation product of hypotaurine – taurine, showed impaired hypotaurine synthesis and growth arrest. Tumor burden nude mice fed with taurine rich food exhibited tumor growth inhibition. Hypotaurine is another oncometabolite discovered afterα-hydroxyglutarate in glioma. The abovementioned results has been published in Oncotarget (2016 Feb 25. doi: 10.18632/oncotarget.7710.) recently.
DICP Researchers Find a New Pathological Mechanism of Glioma Centered in Hypotaurine Through Functional Metabolomics Research (Photo by Peng Gao)
Functional metabolomics, based on the traditional metabolomics focusing on differential metabolite discovery, integrates molecular and cellular biology, bioinformatics, in silico modeling techniques and so on to probe the functions of the important differential metabolites in specific biological and pathological backgrounds. It is the development and innovation of traditional metabolomics. Since the setup of the Metabolomics Research Center and the Scientific Center for Translational Medicine, DICP has the ability to carry out functional metabolomics research with respect to scientists and platform. The success of 39th DICP symposium on functional metabolomics held in Nov., 2015 facilitates the expansion of functional metabolomics internationally. Hypotaurine discovered as an oncometabolite in glioma is one of our typical achievements in functional metabolomics studies (Text/Photo by Peng Gao) .