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The dual lipid desaturase/hydroxylase DEGS2 controls phytoceramide levels necessary to counter intestinal inflammation

ABSTRACT: The dual lipid desaturase/hydroxylase DEGS2 controls phytoceramide levels necessary to counter intestinal inflammation

PROVIDER: PRJNA986438 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24988755_1.fastq.gz	Fastqsanger.gz
	SRR24988755_2.fastq.gz	Fastqsanger.gz
	SRR24988756_1.fastq.gz	Fastqsanger.gz
	SRR24988756_2.fastq.gz	Fastqsanger.gz
	SRR24988757_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

The dual lipid desaturase/hydroxylase DEGS2 controls phytoceramide levels necessary to counter intestinal inflammation

Project description:Intestinal immunity is dependent on barrier function to maintain quiescence. The mechanisms for the maintenance of this barrier are not fully understood. Delta 4-desaturase, Sphingolipid 2 (DEGS2) is a lipid desaturase and hydroxylase, which catalyzes the synthesis of ceramide and phytoceramide from dihydroceramide. Using a forward genetic approach, we found and validated a mutation in Degs2 as causative in increasing susceptibility to colitis and altering the phytoceramide balance in the colon. DEGS2 is expressed in the intestinal epithelium, and the colitis phenotype is dependent on the non-hematopoietic compartment of the mouse. In the absence of DEGS2, the colon lacks phytoceramides and accumulates large amounts of the precursor lipid dihydroceramide. In response to DSS induced colitis, colonic epithelial cells in DEGS2-deficient mice had increased cell death and decreased proliferation compared to those in wildtype mice. These findings demonstrate that DEGS2 is needed to maintain epithelial integrity, protect against DSS-induced colitis and maintain lipid balances in vivo.

2023-08-24 | GSE235544 | GEO

The dual lipid desaturase/hydroxylase DEGS2 controls phytoceramide levels necessary to counter intestinal inflammation.

Project description:Intestinal immunity is dependent on barrier function to maintain quiescence. The mechanisms for the maintenance of this barrier are not fully understood. Delta 4-desaturase, sphingolipid 2 (DEGS2) is a lipid desaturase and hydroxylase that catalyzes the synthesis of ceramide and phytoceramide from dihydroceramide. Using a forward genetic approach, we found and validated a mutation in Degs2 as causative of increasing susceptibility to colitis and altering the phytoceramide balance in the colon. DEGS2 is expressed in the intestinal epithelium, and the colitis phenotype is dependent on the non-hematopoietic compartment of the mouse. In the absence of DEGS2, the colon lacks phytoceramides and accumulates large amounts of the precursor lipid dihydroceramide. In response to dextran sodium sulfate (DSS)-induced colitis, colonic epithelial cells in DEGS2-deficient mice had increased cell death and decreased proliferation compared to those in wild-type mice. These findings demonstrate that DEGS2 is needed to maintain epithelial integrity, protect against DSS-induced colitis and maintain lipid balance in vivo.

| S-EPMC10499023 | biostudies-literature

N-hydroxylase

Project description:N-hydroxylase

| PRJEB82622 | ENA

Counter-diffusion DNBR

Project description:Counter-diffusion DNBR Raw sequence reads

| PRJNA1146795 | ENA

Bacterial stigmasterol degradation involving radical flavin delta-24 desaturase and molybdenum-dependent C26 hydroxylase

Project description:Sterols are ubiquitous membrane constituents that persist to a large extent in the environment due to their water insolubility and chemical inertness. Recently, an oxygenase-independent sterol degradation pathway was discovered in a cholesterol-grown denitrifying bacterium Sterolibacterium (S.) denitrificans. It achieves hydroxylation of the unactivated primary C26 of the isoprenoid side chain to an allylic alcohol via a phosphorylated intermediate in a four-step ATP-dependent enzyme cascade. However, this pathway is incompatible with the degradation of widely distributed steroids containing a double bond at C-22 in the isoprenoid side chain such as the plant sterol stigmasterol. Here, we have enriched a prototypical delta-24 desaturase from S. denitrificans, which catalyses the electron acceptor-dependent oxidation of the intermediate stigmast-1,4-diene-3-one (SDO) to a conjugated 22,(E)24-diene. We suggest an 44 architecture of the 440 kDa enzyme, with each subunit covalently binding an FMN cofactor to a histidyl residue. As isolated, both flavins are present as red semiquinone radicals, which can be reduced by SDO but cannot be oxidised even with strong oxidising agents. We propose a mechanism involving an allylic radical intermediate in which two flavin semiquinones each abstract one hydrogen atom from the substrate. The conjugated delta-22,24 moiety formed allows for the subsequent hydroxylation of the terminal C26 with water by a heterologously produced molybdenum-dependent steroid C26 dehydrogenase. In conclusion, the pathway elucidated for delta-22 steroids achieves oxygen-independent hydroxylation of the isoprenoid side chain by bypassing the ATP-dependent formation of a phosphorylated intermediate.

2024-05-21 | PXD048763 | Pride

A novel Tetrahymena thermophila sterol C-22 desaturase belongs to the fatty acid hydroxylase/desaturase superfamily.

Project description:Sterols in eukaryotic cells play important roles in modulating membrane fluidity and in cell signaling and trafficking. During evolution, a combination of gene losses and acquisitions gave rise to an extraordinary diversity of sterols in different organisms. The sterol C-22 desaturase identified in plants and fungi as a cytochrome P-450 monooxygenase evolved from the first eukaryotic cytochrome P450 and was lost in many lineages. Although the ciliate Tetrahymena thermophila desaturates sterols at the C-22 position, no cytochrome P-450 orthologs are present in the genome. Here, we aim to identify the genes responsible for the desaturation as well as their probable origin. We used gene knockout and yeast heterologous expression approaches to identify two putative genes, retrieved from a previous transcriptomic analysis, as sterol C-22 desaturases. Furthermore, we demonstrate using bioinformatics and evolutionary analyses that both genes encode a novel type of sterol C-22 desaturase that belongs to the large fatty acid hydroxylase/desaturase superfamily and the genes originated by genetic duplication prior to functional diversification. These results stress the widespread existence of nonhomologous isofunctional enzymes among different lineages of the tree of life as well as the suitability for the use of T. thermophila as a valuable model to investigate the evolutionary process of large enzyme families.

| S-EPMC9485055 | biostudies-literature

RNAseq Quantitative Analysis of Arabidopsis Wild Type versus flavonoid 3' hydroxylase tt7 mutant

Project description:Transcriptome of seeds at eight days after polinization were compared between wild type and loss-of-function mutant in the flavonoid 3' hydroxylase TT7 gene

2023-05-31 | GSE197932 | GEO

Modifier Genes in 21-hydroxylase Deficiency - GSD 5607

Project description:Modifier Genes in 21-hydroxylase Deficiency - GSD 5607

| PRJNA377375 | ENA

GENE-counter, a computational and statistical pipeline for assessing RNA-Seq data for genome-wide expression differences

Project description:RNA-Sequencing is a transformative method that captures the quantitative dynamics of a transcriptome with exquisite sensitivity and single-base resolution. There are, however, few computational pipelines for RNA-Seq with statistical tests that evince sufficient robustness and power as demanded by the difficult combination of small sample sizes and high variability in sequence read counts. To this end, we developed GENE-counter, a complete software pipeline for analyzing RNA-Seq data for genome-wide expression differences between replicated treatment groups. One important component of GENE-counter is a statistical test based on the NBP parameterization of the negative binomial distribution for identifying differentially expressed genome features. We used GENE-counter to analyze RNA-Seq data derived from Arabidopsis thaliana infected with a strain of defense-eliciting bacteria. We identified 308 genes that were differentially induced. Using alternative methods, we provided support for the induced expression and biological relevance of a substantial proportion of the genes. These results suggest the NBP parameterization of the negative binomial distribution is well suited for explaining RNA-Seq data and the statistical test makes GENE-counter a powerful pipeline for studying genome-wide expression changes. GENE-counter is freely available at http://changlab.cgrb.oregonstate.edu/. Our RNA-seq data is uploaded on the NCBI short read archive (SRA) under the SRA025952.

2010-12-03 | GSE25818 | GEO

Stearoyl-CoA desaturase mediated monounsaturated fatty acid availability supports humoral immunity

Project description:Immune cells can metabolize fatty acids (FAs) to generate energy. The source of different fatty acid species, and their impacts on humoral immunity remains poorly understood. Here we report that proliferating B cells require increased amount of monounsaturated fatty acids (MUFA) to maintain mitochondrial metabolism and mTOR activity, and to prevent excessive autophagy and endoplasmic reticular (ER) stress. Furthermore, B cell extrinsic Stearoyl-Coa desaturase (SCD) activity generates endogenous MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.

2020-12-02 | GSE162460 | GEO

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