Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA309409 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3111450.fastq.gz | Fastqsanger.gz | |||
| SRR3111460.fastq.gz | Fastqsanger.gz | |||
| SRR3111470.fastq.gz | Fastqsanger.gz | |||
| SRR3111480.fastq.gz | Fastqsanger.gz | |||
| SRR3111451.fastq.gz | Fastqsanger.gz |
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Project description:Liver of MAT1A WT and MAT1A KO mice treated with placebo or SAMe during 8 weeks
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Project description:Gene expression analysis of the liver of MAT1A WT and MAT1A KO mice treated with placebo or SAMe during 8 weeks
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Project description:Methionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
2017-02-02 | GSE77082 | GEO
Project description:Methionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
2017-02-02 | GSE77079 | GEO
Project description:Using Affymetrix data analysis, important signalling pathways and transcription factors relevant to gut inflammation and anti-inflammatory action of probiotics were identified using the clinically validated probiotic VSL#3 and the IL10-knockout mouse, an animal model for inflammatory bowel disease. VSL#3 increased expression of genes in volved in PPAR signalling and metabolism of xenobiotics and decreased expression of genes involved in immune response/inflammatory response. IL10-knockout (IL10-KO) and wildtype (WT) mice housed under specific pathogen free (SPF) conditions were sacrificed at 24 weeks by cervical dislocation. The study is comprised of two independent Microarray experiments. Microarray experiment1 compares gene expression of IL10-KO and WT colon tissue. For microarray analysis RNA was extracted from the colon tissue of each mouse (WT n=7, IL10-KO n=6). Microarray experiment2 compares gene expression of WT and IL10-KO mice fed with either placebo or probiotic VSL#3. IL10-KO and WT mice were fed with placebo or 1.3x109 cfu of lyophilized VSL#3 bacteria post weaning for 21 weeks. For microarray analysis RNA was extracted from the caecum tissue of each mouse (WT Placebo n=6, IL10-KO Placebo n=6, IL10-KO VSL#3 n=6).
2010-05-15 | E-GEOD-13819 | biostudies-arrayexpress
Project description:Adult (12 weeks old) WT, LKO and KO male mice from C57Bl6J were either treated with a control diet (CTRL) or an High Fat Diet (HFD) during 12 weeks prior to liver gene expression analysis
2018-12-05 | GSE123354 | GEO
Project description:Hepatocyte Nuclear Factor 4 alpha (HNF4α), a master regulator of hepatocyte differentiation, and circadian regulator Aryl Hydrocarbon-Like Receptor-Like 1 (ARNTL, or BMAL1) though robustly co-expressed in healthy liver, are incompatible within the context of HCC. Differential expression of Bmal1 and Hnf4α may control susceptibility to liver disease and ultimately, hepatocellular carcinoma. We compared gene expression profiles under conditions of inducible loss of hepatic Hnf4α and inducible loss of Hnf4a and Bmal1 in this RNA-seq experiment. Hepatic Hnf4a (H-KO) or Hnf4a and Bmal1 (BH-KO) were inducibly knocked out after 5 days tamoxifen treatment in eight week-old mice (H-KO) or (BH-KO) followed by vivarium chow or high fat feeding (BH-HF-KO). Littermate control mice (H-WT, BH-WT and BH-HF-WT ) were also treated with tamoxifen at eight weeks of age, but since they lacked the Cre transgene, Hnf4a and Bmal1 expression remained intact. Livers were harvested at 10 weeks of age (BH-WT/KO, H-WT/KO) or 45 weeks ( BH-HF-WT/KO) of age after high fat diet feeding, and liver tissue was flash frozen in liquid nitrogen.
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Project description:One-carbon metabolism is a universal hub for cellular metabolism and epigenetic regulation.1–3 Here, we report that formaldehyde (FA), a one-carbon unit that organisms produce in substantial quantities through folate metabolism,4 is a regulator of the one-carbon cycle via the biosynthesis of S-adenosyl-L-methionine (SAM), an essential one-carbon building block for synthesis of nucleotides, amino acids, and methylated nucleic acids and proteins.5 Activity-based protein profiling (ABPP) in mouse liver tissue identifies FA-sensitive cysteine sites across the proteome, revealing several one-carbon cycle targets including S-adenosylmethionine synthetase isoform 1 (MAT1A), the terminal enzyme in SAM biosynthesis. Biochemical studies of the formaldehyde-MAT1A interaction establish FA-dependent inhibition of MAT1A activity through a conserved C120 site, as the MAT2A isoform lacking this cysteine is not FA-sensitive. CRISPR knockout-generated HepG2 cell models that predominantly express either MAT1A or MAT2A show that MAT1A-positive cells respond to FA treatment in a dose-dependent manner by decreasing their SAM levels and downstream RNA methylation, whereas the MAT2A-positive cells are not affected by FA. Our findings reveal an unexpected interplay between SAM and FA, two central one-carbon units to influence the overall methylation potential of the cell.
2023-11-02 | PXD018251 | Pride
Project description:S-adenosylmethionine (SAMe) is the principal methyl donor synthesized by methionine adenosyltransferase 1A (MAT1A)-encoded enzyme in the liver. Mice lacking Mat1a have hepatic SAMe depletion, spontaneous development of non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). To understand how SAMe depletion drives liver pathologies we performed phospho-proteomics in Mat1a knockout (KO) mice livers and the most striking change was hyperphosphorylation of La-Related Protein 1 (LARP1), which in the unphosphorylated form negatively regulates translation of 5'-terminal oligopyrimidine (TOP)-containing mRNAs. Consistently, multiple TOP proteins are induced in the KO livers. We identified LARP1-T449 as a novel, SAMe-sensitive phospho-site of cyclin-dependent kinase 2. LARP1-T449 phosphorylation induced global translation, cell growth, migration, invasion, and expression of oncogenic TOP-ribosomal proteins in HCC cells. LARP1 expression is increased in human NASH and HCC. Our results reveal a novel SAMe-sensitive mechanism of LARP1 phosphorylation that may be involved in the progression of NASH to HCC.
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