The role of Gch1 in the macrophage response to LPS
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE112720 | GEO | 2018/11/30
REPOSITORIES: GEO
Similar Datasets
Project description:Inducible nitric oxide synthase (iNOS) plays a crucial role in controlling growth of mycobacteria, presumed to be via nitric oxide (NO) mediated killing. However, NOS enzymes can also signal through NO-independent pathways, and production of NO by NOS requires the cofactor tetrahydrobiopterin (BH4). We compared Nos2-/- mice to mice with macrophage BH4 deficiency (Gch1fl/flTie2cre), due to a leukocyte-specific deletion of Gch1, to uncover the specific contribution of NO-independent NOS functions to anti-mycobacterial immunity. We used microarrays to detail the global programme of gene expression in uninfected and BCG infected macrophages that were either deficient in iNOS (Nos2-/- vs C57bl6/J) or BH4/Gch1 (GCHfl/flTie2cre vs GCHfl/fl)
2018-11-30 | GSE107543 | GEO
Project description:To investigate the physiological role of BH4 in cardiac function, we developed mice with cardiomyocyte-specific deletion of (cm)Gch1, the gene that encodes for GTPCH, which responsible for de novo synthesis of BH4. We performed RNA sequencing in heart tissues from cmGch1 KO and WT mice.
2024-04-24 | GSE206063 | GEO
Project description:The role of Gch1 in the macrophage response to LPS
| PRJNA448785 | ENA
Project description:Guanosine triphosphate cyclohydrolase I (GCH1) was previously identified as a regulator of reactive oxygen species (ROS) in brain tumor initiating cells (BTICs). Elucidating the GCH1/Tetrahydrobiopterin (BH4) pathway in BTICs has unveiled the necessity for GCH1 to protect BTICs from lipid peroxidation. Within this study, we observed differences in lipid pathways and lipid metabolites during GCH1 modulation. Alteration to polyunsaturated fatty acids (PUFAs), a species of oxidatively vulnerable lipids, were altered during GCH1 knockdown. Pharmacological inhibition of BH4 with drugs known to cross the blood brain barrier (sulfasalazine and pyrimethamine) successfully reduced growth in GCH1 overexpressed BTICs, induced lipid peroxidation.
2024-12-01 | GSE251878 | GEO
Project description:We conducted high-throughput sequencing and bioinformatics analysis of GCH1-KD BV2 microglial cells treated with adenovirus. Their RNA was extracted and analyzed, and the results were verified by quantitative real-time polymerase chain reaction (PCR). This study explored the lncRNAs, miRNAs, circRNAs and mRNAs regulated by GCH1 and revealed a possible mechanism of GCH1 in microglia activation.
2023-01-31 | GSE164836 | GEO
Project description:We conducted small RNA sequencing and bioinformatics analysis of GCH1-KD BV2 microglial cells treated with adenovirus. Their RNA was extracted and analyzed, and the results were verified by quantitative real-time polymerase chain reaction (qRT-PCR). This study explored the miRNAs and mRNAs regulated by GCH1 and revealed a possible mechanism of GCH1 in microglial activation.
2023-01-05 | GSE165204 | GEO
Project description:The experiments were done using an Orbitrap Fusion or an Orbitrap Fusion Lumos mass spectrometer. Multiplexing was achieved using either TMT10 or TMT11 reagents and the SPS-MS3 method. Basic pH reversed-phase chromatography (bRPLC) was used for off-line pre-fractionation; 12 fractions were analyzed for proteome mappings (PMID: 26700037) and 24 fractions plus a phosphotyrosine-enriched sample for phosphoproteome mappings (PMID: 31606085). Phosphoproteome mappings were done using both HCD fragmentation with Orbitrap fragment ion detection and CID fragmentation with ion trap fragment ion detection (PMID: 29487189, PMID: 31606085). If multiple TMT sets were required to analyze all samples from an experiment two bridge channels pooled from all samples was used to connect the data from the individual TMT sets (PMID: 28892078).
Five proteomics experiments are described in the paper:
(i) 1. Quantitative proteomics of fully polarized macrophages after 4 days of treatment with IL4 or IFNgamma/LPS to determine global proteome landscape of fully polarized THP-1-derived M1-type versus M2a-type macrophages:
Proteome mapping on Orbitrap Fusion (one TMT set)
RAW files: Marneros_4DayTreatment_proteome_fraction01 to ...fraction12
8 samples
Labeling: PMA.1 (126), PMA.2 (127n), IL4.1 (127c), IL4.2 (128n), ILJQ1.1 (128c), ILJQ1.2 (129n), IFNgamma.1 (129c), IFNgamma.2 (130n)
(ii) Time-course quantitative proteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify protein changes associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization:
Proteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03)
RAW files:
Marneros_timecourse_proteome_TMTset01_fraction01 to ...fraction12
Marneros_timecourse_proteome_TMTset02_fraction01 to ...fraction12
Marneros_timecourse_proteome_TMTset03_fraction01 to ...fraction12
22 samples
Labeling:
set01; bridge 1 (126), PMA 0min (127n), PMA 10min (127c), PMA 30min (128n), PMA 1h (128c), PMA 2h (129n), PMA 4h (129c), PMA 8h (130n), PMA 24h (130c), bridge 2 (131n)
set02; bridge 1 (126), IL4 10min (127n), IL4 30min (127c), IL4 1h (128n), IL4 2h (128c), IL4 4h (129n), IL4 8h (129c), IL4 24h (130n), IFN 10min (130c), bridge 2 (131n)
set03; bridge 1 (126), IFN 30min (127n), IFN 1h (127c), IFN 2h (128n), IFN 4h (128c), IFN 8h (129n), IFN 24h (129c), bridge 2 (131n)
(iii) Time-course quantitative phosphoproteomics during the first 24 hours after induction of macrophage polarization in THP-1-derived macrophages to identify phosphorylation events associated with M1-type (IFNgamma/LPS-induced) versus M2a-type (IL-4-induced) polarization (same time points as in group 2):
Phosphoproteome mapping on Orbitrap Fusion (three TMT sets: set01, set02, set03)
RAW files:
Marneros_timecourse_phospho_TMTset01_fraction01 to ...fraction06, ...fraction08 to ...fraction24, ...pY
Marneros_timecourse_phospho_TMTset02_fraction01 to ...fraction12, ...fraction16 to ...fraction24, ...pY
Marneros_timecourse_phospho_TMTset03_fraction01 to ...fraction24, ...pY
The following RAW files gave no phosphopeptide quantifications (they are no included in the group of provided RAW files): set01_fraction07, set02_fraction13, set02_fraction14, set02_fraction15.
22 samples
Labeling: as in (ii)
(iv) Quantitative proteomics to assess the effects of the B-Raf inhibitor GDC-0879 or of the MEK inhibitor trametinib on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment:
Proteome mapping on Orbitrap Fusion (one TMT set)
RAW files: Marneros_BRAF_inhibitor_proteine_fraction01 to ...fraction12
11 samples
Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (131n), IL4+GDC 2 (128n), IL4+TRAM 1 (130c), IL4+TRAM 2 (129n), IFNgamma+LPS 1 (130n), IFNgamma+LPS 2 (127c), IFNgamma+LPS+TRAM 1 (126), IFNgamma+LPS+TRAM 2(129c), IFNgamma+LPS+GDC (128c)
(v) Quantitative phosphoproteomics to assess the effects of the B-Raf inhibitor GDC-0879 on IL-4-induced M2-type polarization and IFNgamma/LPS-induced M1-type polarization on THP-1-derived macrophages after 24 hours of treatment:
Phosphoproteome mapping on Orbitrap Fusion Lumos (one TMT set)
RAW files: Marneros_BRAF_inhibitor_phospho_fraction01 to ...fraction24, ...pY
7 samples
Labeling: IL4 1 (131c), IL4 2 (127n), IL4+GDC 1 (130n), IL4+GDC 2 (128n), IFNgamma+LPS 1 (128c), IFNgamma+LPS 2 (127c), IFNgamma+LPS+GDC (130c)
2019-12-10 | MSV000084672 | MassIVE
Project description:Parkinson’s disease (PD) is one of the most common neurodegenerative disorders with high disability. Hyposecretion of dopamine (DA) is the final pathological outcome of PD occurrence. Unfortunately, safe and efficient therapeutic drugs are deficient. Tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis, could hydroxylate tyrosine and generate levodopa with tetrahydrobiopterin (BH4) as an indispensable coenzyme. Moreover, BH4 was confirmed to confer neuroprotection against PD. Thus, regulation of BH4 synthesis is verified to become a promising therapeutic strategy for PD. Here, this present study exhibited that artemisinin (ART) effectively produced neuroprotection against PD. Then, the combined analysis of midbrain proteomics with non-targeted metabolomics indicated that ART might target adenylate cyclase 5 (Adcy5) to increase GTP cyclohydrolase 1 (Gch1, BH4 synthetase) expression to further promote BH4 synthesis. To test this hypothesis, molecular docking showed that ART could bind to Adcy5 d
2023-07-06 | PXD043573 |
Project description:Hypoxia-inducible factor 1-alpha (HIF1a) is a basic helix-loop-helix PAS domain-containing protein, and is considered as the master transcriptional regulator of cellular response to hypoxia and inflammatory stimuli. Studies over the year have demonstrated that HIF1a play a critical role in innate immune cell response to infection and injury. Here we isolated bone marrow of 3 mice per group (Lyz2cre and Lyz2cre:HIF1aFl/Fl) and differentiated into macrophages by culturing them in M-CSF containing media. These cells were stimulated with 100ng/ml LPS, 10ng/ml IFNgamma, 10ng/ml IL4 or 10ng/ml IL10 for 18 hours. Total RNA was isolated and subjected to RNAseq analyses.
2021-03-05 | GSE131364 | GEO
Project description:Bone marrow derived dendritic cells were generated from Ubc9[fl;-] and Ubc9[+/+] mice. After in vitro derivation in the presence of GM-CSF, dendritic cells were treated with tamoxifen for four days to cause CreERT2 activation, and induce Ubc9 floxed allele deletion. This allowed comparative transcriptomic analysis of Ubc9[+/+] and Ubc9[-/-] dendritic cells unstimulated or stimulated with 10ng/ml LPS for one hour and six hours.
2015-12-14 | GSE66178 | GEO