Project description:We studied the effects of polyamine pathway inhibitors on differentiation of nonpathogenic Th17 cellsin vitro. Here, we used difluoromethylornithine (DFMO), an irreversible inhibitor of ODC1, the enzyme that catalyzes the conversion of ornithine to putrescine.
2021-07-06 | GSE165088 | GEO
Project description:Characterization of the fungal community living with the laboratory-cultured harmful alga Karlodinium veneficum (Dinophyceae) from different original sources
Project description:Polyamines (putrescine, spermidine, and spermine) are major organic polycations essential for a wide spectrum of cellular processes. The cells require mechanisms to maintain homeostasis of intracellular polyamines to prevent otherwise severe adverse effects. We performed a detailed transcriptome profile analysis of P. aeruginosa in response to agmatine and putrescine with an emphasis in polyamine catabolism. Agmatine serves as precursor compound for putrescine (and hence spermidine and spermine), which was proposed to convert into GABA and succinate before entering the TCA cycle in support of cell growth as the sole source of carbon and nitrogen. Two acetylpolyamine amidohydrolases, AphA and AphB, were identified to be involved in the conversion of agmatine into putrescine. Enzymatic products of AphA were confirmed by mass spectrometry analysis. Interestingly, the alanine-pyruvate cycle was shown indispensable for polyamine utilization. The newly identified dadRAX locus, encoding the regulator, alanine transaminase and racemase respectively, coupled with SpuC, the major putrescine-pyruvate transaminase, were key components to maintain alanine homeostasis. Corresponding mutant strains were severely hampered in polyamine utilization. On the other hand, the alternative gamma-glutamylation pathway for the conversion of putrescine into GABA was also discussed. Subsequently, GabD, GabT and PA5313 were identified for GABA utilization. Growth defect of PA5313 gabT double mutant in GABA suggested the importance of these two transaminases. The succinic-semialdehyde dehydrogenase activity of GabD and its induction by GABA was also demonstrated in vitro. Polyamine utilization in general was proven independent of the PhoPQ two-component system even the expression of which was induced by polyamines. Multiple potent catabolic pathways as depicted in this study could serve pivotal roles in control of intracellular polyamine levels. Keywords: Metabolism, polyamines, agmatine, putrescine, glutamate, phoPQ.
Project description:We studied the effects of polyamine pathway inhibitors on differentiation of pathogenic and nonpathogenic Th17 cells in vitro. Here, we used difluoromethylornithine (DFMO), an irreversible inhibitor of ODC1, the enzyme that catalyzes the conversion of ornithine to putrescine.