Metabolites changes related to glucose-mediated energy production in chemotheraphy-induced cachexia
Ontology highlight
ABSTRACT:
ORGANISM(S): Mouse Mus Musculus
TISSUE(S): Blood
DISEASE(S): Cachexia
SUBMITTER: 
Hyun Ju Yoo
PROVIDER: ST001467 | MetabolomicsWorkbench | Tue Aug 18 00:00:00 BST 2020
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Osteolytic lesions with suppression of osteoblastic (OB) differentiation are hallmarks of multiple myeloma (MM). Most recently, Gln availability has been found to be essential to sustain bone mass formation in murine models. On the other hand, MM cells are Gln-addicted and consume huge amounts of the amino acid, leading to a partial Gln depletion in the bone marrow (BM) plasma. We hypothesize that MM-dependent Gln depletion contributes to the defective OB differentiation characteristic of MM. Conversely, GLS (both KGA and GAC isoforms) and SLC38A2, the gene for the concentrative Gln transporter SNAT2, were induced. Consistent with this conclusion, the activity of SNAT2 was absent in undifferentiated hMSCs but well detectable after 14 days of OB differentiation, when total Gln uptake was also increased. Under the same conditions, OB differentiation markers (RUNX2, COL1A1, ALPL expression and ALPL activity or staining) were significantly induced but their expression was blunted by incubation in low-Gln (0.4 mM) medium or in the presence of the SNAT2 inhibitor MeAIB. The incubation in Gln-free D-MEM suppressed the induction of GLS and SLC38A2 along with OB differentiation, which was restored by the supplementation of Non-Essential Amino Acids (NEAA). Among NEAA, only asparagine (Asn) was able to rescue OB differentiation in the absence of Gln. The determination of intracellular amino acids with MS indicated that OB differentiation was associated with the increase of cell Asn, without significant changes of Gln, glutamate (Glu) or aspartate (Asp). Asparagine Synthetase (ASNS), the Gln-dependent enzyme that accounts for Asn synthesis, was also found induced during OB differentiation of hMSCs. Gene Expression Profiles of primary BM hMSCs and OBs from bone biopsies of both healthy donors and MM patients indicated that GLS, ASNS, and SLC38A2 are more expressed in OBs, while the expression of GLUL, the gene for GS, is higher in undifferentiated hMSCs from healthy donors. Overall, these results indicate that (1) OB differentiation of hMSCs is Gln-dependent; (2) the partial Gln depletion, imposed by Gln-addicted MM cells in the BM microenvironment, contributes to the impairment of osteoblastic differentiation of hMSCs; (3) hindrance of differentiation may depend on the limited availability of intracellular Asn derived from Gln-dependent ASNS. These results support the evidence that Gln addiction of MM cells affects bone microenvironment leading to the inhibition of OB differentiation and, consequently, to the development of MM bone disease.
2020-12-01 | GSE147791 | GEO
Project description:Amino acid starvation during recombinant protein production (RPP) induces metabolic stress to cellular host which results in reduced productivity of the recombinant bioprocess. In present study, supplementation of amino acids in a chemically defined medium showed several folds increase in recombinant product titers in E. coli BL21 DE3 strain. To understand, the effect of amino acid supplementation in alleviating cellular stress during RPP a deep insight of cellular physiology must be studied. Here, we performed transcriptomic analysis of E. coli expressing a recombinant protein in two different conditions: with (5 mM of all 20 amino acids) as test and without supplementation of amino acids as control. RNA-seq data revealed downregulation of several genes associated with stress in test culture confirming the critical role of amino acids supplementation in improving RPP.
2020-05-18 | GSE138044 | GEO
Project description:Campylobacter jejuni is one of the most important causes of food-borne diseases in industrialized countries. It is known that amino acids are important nutrient source for this pathogen, because C. jejuni lacks enzymes related to glycolysis. However, the characteristics on metabolism of C. jejuni grown in the nutrient restricted medium with a specific amino acid is not fully elucidated. This study shows that C. jejuni NCTC11168 grew well in the nutrient restricted medium containing serine, aspartate, glutamate, and proline. The single subtraction of serine significantly reduced the growth, while three other amino acids did not, suggesting the priority of serine among the four amino acids. In the transcriptomic analysis of C. jejuni NCTC11168 grown in medium with serine as a main energy source. Serine seemed to be sensed by some chemoreceptors and the C. jejuni might reached an adaptation stage with active growth. That is, the expression of flagellar assembly components was downregulated and the biosynthesis of multiple amino acids and nucleotide sugars were upregulated. These data suggest the higher requirement of serine as a nutrient of C. jejuni NCTC11168.
2018-09-17 | GSE119472 | GEO
Project description:Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pool. In this study, an Agilent customized microarray representing approximately 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses. Amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to pulses of valine, glutamate, and glutamine, respectively, and Val-, Glu and Gln-specific genes were further distinguished from them. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, hierarchical clustering and enrichment of functional categories. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector. Three amino acids (Glutamate, Glutamine, and Valine) were adopted to perturb the culture of subtilis. Four time-points were investigated for each perturbation. There are two replicates for the first time-point of Valine-treatment experiment.
2010-05-05 | E-GEOD-17243 | biostudies-arrayexpress
Project description:Algal biofuel production requires an input of synthetic nitrogen fertilizer. Fertilizer synthesized via the Haber-Bosch process produces CO2 as a waste by-product and represents a substantial financial and energy investment. Reliance on synthetic fertilizer attenuates the environmental significance and economic viability of algae production systems. To lower fertilizer input, the waste streams of algal production systems can be recycled to provide alternative sources of nitrogen such as amino acids to the algae. The halophytic green alga Dunaliella viridis can use ammonium (NH4+) derived from the abiotic degradation of amino acids, and previously, supplementation of NH4+ from glutamine (GLN) degradation was shown to support acceptable levels of growth and increased neutral lipid production compared to nitrate. To understand the effect of glutamine-released NH4+ on algae growth and physiology, metabolite levels, growth parameters, and transcript profiles of D. viridis cultures were observed in a time course after transition from media containing nitrate as a sole N source to medium containing GLN, glutamate (GLU), or a N-depleted medium. Growth parameters were similar between GLN (NH4+) and nitrate supplemented cultures, however, metabolite data showed that the GLN supplemented cultures (NH4+) more closely resembled cultures under nitrogen starvation (N-depleted and GLU supplementation). Neutral lipid accumulation was the same in nitrate and glutamine-derived NH4+ cultures. However, glutamine-derived NH4+ caused a transcriptional response in the immediate hours after inoculation of the culture. The strong initial response of cultures to NH4+ changed over the course of days to closely resemble that of nitrogen starvation. These observations suggest that release of NH4+ from glutamine was sufficient to maintain growth, but not high enough to trigger a cell transition to a nitrogen replete state. Comparative transcript profiling of the nitrogen-starved and nitrate-supplied cultures show an overall downregulation of fatty acid synthesis and a shift to starch synthesis and accumulation. The results indicate that a continuous, amino acid derived slow release of NH4+ to algae cultures could reduce the amount of synthetic nitrogen needed for growth, but optimization is needed to balance nitrogen starvation and cell division.
2018-03-30 | GSE111548 | GEO
Project description:Exposure to hypoxia disrupts energy metabolism and induces inflammation. However, the pathways and mechanisms underlying energy metabolism disorders caused by hypoxic conditions remain unclear. In this study, we constructed a hypoxic animal model and applied transcriptomic and non-targeted metabolomics techniques to further investigate the pathways and mechanisms of hypoxia exposure that disrupt energy metabolism. Transcriptome results showed that 3007 genes were significantly differentially expressed under hypoxic exposure, and Gene Ontology (GO) annotation analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis showed that the differentially expressed genes (DEGs) were mainly involved in energy metabolism and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathway. Differential genes in the TCA cycle (IDH3A, SUCLA2, and MDH2) and OXPHOS pathway (NDUFA3, NDUFS7, UQCRC1, CYC1, and UQCRFS1) were validated using mRNA and protein expression, and the results showed downregulation. The results of non-targeted metabolomics showed that 365 significant differential metabolites were identified under plateau hypoxia stress. KEGG enrichment analysis showed that the differential metabolites were mainly enriched in metabolic processes, such as energy metabolism, nucleotide metabolism, and amino acid metabolism. Hypoxia exposure disrupted the TCA cycle and reduced the synthesis of amino acids and nucleotides by decreasing the concentrations of cis-aconitate, α-ketoglutarate, NADH, NADPH, most amino acids, purines, and pyrimidines. Bioinformatics analysis was used to identify inflammatory genes related to hypoxia exposure, and some inflammatory genes were selected for verification. We found that the mRNA and protein expression levels of IL1B, IL12B, S100A8, and S100A9 in kidney tissues were upregulated under hypoxic exposure. Our results suggest that hypoxia exposure inhibits the TCA cycle and OXPHOS signalling pathway by inhibiting IDH3A, SUCLA2, MDH2, NDUFFA3, NDUFS7, UQCRC1, CYC1, and UQCRFS1, thereby suppressing energy metabolism, inducing amino acid and nucleotide deficiency, and promoting inflammation, ultimately leading to kidney damage.
2023-08-16 | GSE240049 | GEO
Project description:Metabolomic and transcriptomic analysis of changes in the exponential and stationary phase of Clostridioides difficile after cultivation in casamino acids medium (reference) and supplemented with L-lactate and the connection to toxin production.
2021-01-31 | GSE139354 | GEO
Project description:Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pool. In this study, an Agilent customized microarray representing approximately 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses. Amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to pulses of valine, glutamate, and glutamine, respectively, and Val-, Glu and Gln-specific genes were further distinguished from them. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, hierarchical clustering and enrichment of functional categories. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector.
2009-09-09 | GSE17243 | GEO
Project description:Glutamine (Gln) metabolism has been reported to play an essential role in cancer. However, a comprehensive analysis of its role in lung adenocarcinoma is still unavailable. This study established a novel system of quantification of Gln metabolism to predict the prognosis and immunotherapy efficacy in lung cancer. Further, the Gln metabolism in tumor microenvironment (TME) was characterized and the Gln metabolism-related genes were identified for targeted therapy. We comprehensively evaluated the patterns of Gln metabolism in 513 patients diagnosed with lung adenocarcinoma (LUAD) based on 73 Gln metabolism-related genes. Based on differentially expressed genes (DEGs), a risk model was constructed using Cox regression and Lasso regression analysis. The prognostic efficacy of the model was validated using an individual LUAD cohort form Shandong Provincial Hospital, an integrated LUAD cohort from GEO and pan-cancer cohorts from TCGA databases. Five independent immunotherapy cohorts were used to validate the model performance in predicting immunotherapy efficacy. Next, a series of single-cell sequencing analyses were used to characterize Gln metabolism in TME. Finally, single-cell sequencing analysis, transcriptome sequencing, and a series of in vitro experiments were used to explore the role of EPHB2 in LUAD. Patients with LUAD were eventually divided into low- and high-risk groups. Patients in low-risk group were characterized by low levels of Gln metabolism, survival advantage, “hot” immune phenotype and benefit from immunotherapy. Compared with other cells, tumor cells in TME exhibited the most active Gln metabolism. Among immune cells, tumor-infiltrating T cells exhibited the most active levels of Gln metabolism, especially CD8 T cell exhaustion and Treg suppression. EPHB2, a key gene in the model, was shown to promote LUAD cell proliferation, invasion and migration, and regulated the Gln metabolic pathway. Finally, we found that EPHB2 was highly expressed in macrophages, especially M2 macrophages. It may be involved in the M2 polarization of macrophages and mediate the negative regulation of M2 macrophages in NK cells. This study revealed that the Gln metabolism-based model played a significant role in predicting prognosis and immunotherapy efficacy in lung cancer. We further characterized the Gln metabolism of TME and investigated the Gln metabolism-related gene EPHB2 to provide a theoretical framework for anti-tumor strategy targeting Gln metabolism.
2022-07-31 | GSE209973 | GEO
Project description:Industrial producer of multiple amino acids
| PRJNA307 | ENA