Gene expression data of cSHMT mutant, heterozygous, and wild-type mouse colons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE14645 | GEO | 2009/10/01
SECONDARY ACCESSION(S): PRJNA112307
REPOSITORIES: GEO
Similar Datasets
Project description:Folate-mediated one-carbon metabolism is required for purine, thymidylate, and S-adenosylmethionine synthesis. Impairments in folate metabolism diminish cellular methylation potential and genome stability. Cytoplasmic serine hydroxymethyl transferase (cSHMT) regulates partitioning between thymidylate and SAM biosynthesis. These experiments were designed to determine if mutations in cSHMT led to alterations in gene expression. Keywords: genetic modification RNA was isolated from proximal colons of cSHMT mutant, heterozygous, and wild-type mice raised on a folate-deficient diet. Three colon samples were isolated from each genotype to provide biological replication. Mutant and heterozygous data were then compared pair-wise against wild-type expression data.
2010-03-03 | E-GEOD-14645 | biostudies-arrayexpress
Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. GM-CSF drives the generation of human monocyte-derived macrophages with a potent pro-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with the anti-folate pemetrexed (PMX) on the gene expression profile in LPS-activated GM-CSF-primed human monocyte derived macrophages. The specificity of blocking OCM with the anti-folate PMX was demonstrated with folinic acid.
2021-10-28 | GSE159380 | GEO
Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. GM-CSF drives the generation of human monocyte-derived macrophages with a potent pro-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with the anti-folate pemetrexed (PMX) on the gene expression profile in GM-CSF-primed human monocyte derived macrophages.
2021-10-28 | GSE159349 | GEO
Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with high-doses of the anti-folate methotrexate (MTX) on the gene expression profile in M-CSF-primed human monocyte derived macrophages.
2023-10-16 | GSE186151 | GEO
Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with high-doses of the anti-folate methotrexate (MTX) on the gene expression profile in M-CSF-primed human monocyte derived macrophages during LPS activation.
2023-11-25 | GSE189740 | GEO
Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. Methotrexate (MTX) is an anti-folate drug used for Acute Lymphoblastic Leukemia treatment. We explored the molecular impact of blocking GSK3 a/b on the transcriptional effect of high-doses of MTX in M-CSF-primed human monocyte derived macrophages.
2023-10-01 | GSE185872 | GEO
Project description:Low intracellular folate levels diminish the growth rate of HT-29 human colon cancer cells. This is accompanied by a metabolic shift from cytosolic glycolysis towards mitochondrial oxidative phosphorylation, as demonstrated by a lower lactate production and an increased mitochondrial oxygen consumption rate. To obtain insight in the molecular effects underlying these changes, the steady state gene expression profiles of HT-29 cells with different intracellular folate concentrations were compared. The gene expression profile of HT-29 cells with low intracellular folate levels (grown for 3 weeks in 10 ng/ml folic acid (PGA)) was clearly distinct from that of the other exposure conditions, which provide sufficient intracellular folate levels (100 ng/ml PGA, 10 ng/ml methyltetrahydrofolate (MTHF) or 100 ng/ml MTHF). Intracellular folate deficiency, contrary to expectation, did not lead to major changes in expression of genes involved in energy metabolism. This suggests that the shift towards mitochondrial oxidative phosphorylation is not mediated at the transcription level. Furthermore, only minor changes in the expression of folate metabolism related genes were observed. The changes that were observed were consistent with nucleotide salvage and in agreement with nucleotide need of the slow-growing folate-deficient HT-29 cells. The major observed effects were on cell cycle related gene expression, which was increased and interferon-responsive gene expression, which was reduced. The increase in cell cycle related gene expression seems compensatory to the reduced cell growth. Down-regulation of the interferon-response may be explained by decreased expression of signal transducer and activator of transcription 1 upon folate deficiency. Keywords: dose response, folic acid, HT-29 cells, human
2005-08-13 | GSE3099 | GEO
Project description:This is an SBML version of the folate cycle model model from:
A mathematical model of the folate cycle: new insights into folate homeostasis.
Nijhout HF, Reed MC, Budu P, Ulrich CM
J. Biol. Chem.,2004, 279
(53),55008-16
Reference publication: 15496403
Abstract:
A mathematical model is developed for the folate cycle based on standard biochemical kinetics. We use the model to provide new insights into several different mechanisms of folate homeostasis. The model reproduces the known pool sizes of folate substrates and the fluxes through each of the loops of the folate cycle and has the qualitative behavior observed in a variety of experimental studies. Vitamin B(12) deficiency, modeled as a reduction in the V(max) of the methionine synthase reaction, results in a secondary folate deficiency via the accumulation of folate as 5-methyltetrahydrofolate (the "methyl trap"). One form of homeostasis is revealed by the fact that a 100-fold up-regulation of thymidylate synthase and dihydrofolate reductase (known to occur at the G(1)/S transition) dramatically increases pyrimidine production without affecting the other reactions of the folate cycle. The model also predicts that an almost total inhibition of dihydrofolate reductase is required to significantly inhibit the thymidylate synthase reaction, consistent with experimental and clinical studies on the effects of methotrexate. Sensitivity to variation in enzymatic parameters tends to be local in the cycle and inversely proportional to the number of reactions that interconvert two folate substrates. Another form of homeostasis is a consequence of the nonenzymatic binding of folate substrates to folate enzymes. Without folate binding, the velocities of the reactions decrease approximately linearly as total folate is decreased. In the presence of folate binding and allosteric inhibition, the velocities show a remarkable constancy as total folate is decreased.
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version of this model is available: BIOMD0000000213
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL6655501972 | BioModels
Project description:Morrison1989 - Folate Cycle
The model describes the folate cycle
kinetics in breast cancer cells.
This model is described in the article:
Folate cycle kinetics in
human breast cancer cells.
Morrison PF, Allegra CJ.
J. Biol. Chem. 1989 Jun; 264(18):
10552-10566
Abstract:
A mathematical description of polyglutamated folate kinetics
for human breast carcinoma cells (MCF-7) has been formulated
based upon experimental folate, methotrexate (MTX), purine, and
pyrimidine pool sizes as well as reaction rate parameters
obtained from intact MCF-7 cells and their enzyme isolates. The
schema accounts for the interconversion of highly
polyglutamated tetrahydrofolate, 5-methyl-FH4, 5-10-CH2FH4,
dihydrofolate (FH2), 10-formyl-FH4 (FFH4), and 10-formyl-FH2
(FFH2), as well as formation and transport of the MTX
polyglutamates. Inhibition mechanisms have been chosen to
reproduce all observed non-, un-, and pure competition
inhibition patterns. Steady state folate concentrations and
thymidylate and purine synthesis rates in drug-free intact
cells were used to determine normal folate Vmax values. The
resulting average-cell folate model, examined for its ability
to predict folate pool behavior following exposure to 1 microM
MTX over 21 h, agreed well with the experiment, including a
relative preservation of the FFH4 and CH2FH4 pools. The results
depend strongly on thymidylate synthase (TS) reaction
mechanism, especially the assumption that MTX di- and
triglutamates inhibit TS synthesis as greatly in the intact
cell as they do with purified enzyme. The effects of cell cycle
dependence of TS and dihydrofolate reductase activities were
also examined by introducing G- to S-phase activity ratios of
these enzymes into the model. For activity ratios down to at
least 5%, cell population averaged folate pools were only
slightly affected, while CH2FH4 pools in S-phase cells were
reduced to as little as 10% of control values. Significantly,
these folate pool dynamics were indicated to arise from both
direct inhibition by MTX polyglutamates as well as inhibition
by elevated levels of polyglutamated FH2 and FFH2.
Note: two flow BCs were converted into two downstream
concentration BCs, thus removing the GAR and dUMP state
variables. This dropped the number of ODEs from 21 to 19.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000018.
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BioModels Database:
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quantitative kinetic models.
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2005-06-29 | BIOMD0000000018 | BioModels