Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling

Abstract

Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy.

Cyclosporine a directly affects human and mouse b cell migration in vitro by disrupting a hIF-1 αdependent, o2 sensing, molecular switch

“…The differential expression analysis also identified signaling pathways responding to hypoxia and their key regulators. Several of these pathways are associated with HIF-1α, in agreement with findings of other groups [60][61][62][63]. However, several of the proteins reversing the effect of hypoxia with drug had lower fold-changes upon treatment with CyA.…”

Cyclosporine A Directly Affects Human and Mouse B cell Migration in vitro by Disrupting a HIF-1α Dependent, O2 Sensing, Molecular Switch

“…The differential expression analysis identified signaling pathways responding to hypoxia and their key regulators. Several of the identified pathways are associated with HIF-1α, in consensus with the previous literature (70)(71)(72)(73). However, several of the proteins reversing the effect of hypoxia with drug had lower fold-changes upon treatment with CyA.…”

Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease

“…Taurine can cross the blood brain barrier (BBB) and involves in a wide array of physiological phenomena including inhibitory neurotransmission, long-term potentiation in the striatum/hippocampus, and possible protection against glutamate excitotoxicity and prevention of epileptic seizures [46474849]. Interestingly, recent studies on glioma have shown that hypotaurine interferes with hypoxia signaling, leading to malignant phenotypes [5051]. Hypotaurine acts as a competitive inhibitor to activate signals in prolyl hydroxylase domain-2 (PHD2), which regulates hypoxia signals.…”