Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional response of Tetrahymena thermophila to exogenous cholesterol

ABSTRACT: The model ciliate Tetrahymena thermophila satisfies its growth using triterpenoid alcohols, mainly tetrahymanol, as a surrogate of sterols. When sterols are present in the environment, T. thermophila efficiently incorporates and modifies them. T. thermophila can modify exogenous sterols by desaturation at positions C5(6), C7(8) and C22(23), and also by de-ethylation of C24. Three out of four of the enzymes involved in the sterol modification pathway were previously described by our group. However, identification of the sterol C22 desaturase remained elusive, as well as other basic aspects of this metabolism. To get more insights into this peculiar metabolism we here perform a whole transcriptome analysis of T. thermophila in response to exogenous cholesterol. We found 356 T. thermophila genes to be differentially expressed after supplementation with cholesterol for two hours. Among those genes that were upregulated under our experimental conditions, we identified two genes belonging to the long-spaced family of desaturases that we propose as putative sterol C22 desaturases. Moreover, we determined that the inhibition of tetrahymanol synthesis after sensing exogenous cholesterol occurs by a transcriptional downregulation of genes involved in squalene synthesis and cyclization. Finally, we also identified several uncharacterized genes that can be putatively involved in sterols transport and signaling.

ORGANISM(S): Tetrahymena thermophila

PROVIDER: GSE130336 | GEO | 2019/11/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Dietary sterols/steroids and the generalist caterpillar Helicoverpa zea: physiology, biochemistry and midgut gene expression

Project description:Sterols are essential nutrients for insects because, in contrast to mammals, no insect (or arthropod for that matter) can synthesize sterols de novo. Cholesterol is the most common sterol in insects, but it is not found in plants in large quantities; plant-feeding insects typically generate their cholesterol by metabolizing phytosterols. However, different plants species can contain different types of phytosterols, and some phytosterols are not readily converted to cholesterol. In this study we examined, using artificial diets containing single sterols, how typical (cholesterol and stigmasterol) and atypical (cholestanol and cholestanone) sterols/steroids affect the performance of a generalist caterpillar (Helicoverpa zea), restricting this analysis to midgut tissue because this is where sterol/steroid absorption occurs, and the midgut is the putative site of dietary sterol/steroid metabolism. In general, H. zea performed best on the cholesterol and stigmasterol treatments; performance was reduced on cholestanol, and was very poor on cholestanone. We compared the transcript profiles of larval guts in response to differentially suitable sterols, using the optimal sterol, cholesterol, as a control, using a two-color reference design microarray experiment. Midgut gene expression patterns differed between the treatments; relative to cholesterol, differences were lowest on the stigmasterol treatment, intermediate on the cholestanol treatment, and greatest on the cholestanone treatment. Transcriptional profiling comparing Helicoverpa zea gut tissue from third instar larvae exposed to four different dietary sterols, namely Cholesterol (CON), Cholestanol (ChStanol), Cholestan-3-one (Ch3one) and Stigmasterol (Stigma). Two-color reference design. Biological replicates: 4 (5 individuals per replicate). 12 samples total.

2012-06-13 | E-GEOD-38699 | biostudies-arrayexpress

Dietary sterols/steroids and the generalist caterpillar Helicoverpa zea: physiology, biochemistry and midgut gene expression

2012-06-14 | GSE38699 | GEO

Expression of genes in HepG2 cells with Knock-out in cholesterol synthesis

Project description:HepG2 cell line CRISPR-Cas9 generated Knock-out in 4 cholesterol synthesis gene: CYP51, DHCR24, SC5D and HSD17B7 Excess of cholesterol associates with a variety of diseases so its synthesis must be under tight homeostatic control. The early part of cholesterol synthesis with rate-limiting HMGCR and SQLE steps is proceeded by the sterol part where numerous non-polar sterols with poorly defined biological functions are produced. To illuminate their role we developed knockouts (KO) for the consecutive enzymes that metabolize sterols towards cholesterol CYP51A1, DHCR24, SC5D resulted in the accumulation of specific set of sterols in each KO cell. Despite that, we targeted three steps of the cholesterol synthesis housekeeping pathway, the overlap of de-regulated genes was only 9%, suggesting that each set of sterols modulated the hepatic cell transcriptome uniquely. Lanosterol and 24,25-dihydrolanosterol, but not other non-polar sterols, provoked higher cell proliferation, cell cycle changes, and upregulation of metabolic pathways and transcription factors (TFs) associated with cancer progression and immune response like NFKB, SMAD, ESR1 and highly elevated LEF1 a protein from WNT signalling. In contrast, lathosterol and desmosterol caused slower proliferation and apoptosis promotion, through TFs like HNF1A and E2F. We were able to show how sterols from early part of synthesis can promote cell proliferation as sterols from end of synthesis suppress proliferation. These findings challenge the current dogma that sterols produced during cholesterol synthesis have similar biological functions

2024-08-08 | GSE221582 | GEO

Transcriptional response of Tetrahymena thermophila to exogenous cholesterol

Project description:Transcriptional response of Tetrahymena thermophila to exogenous cholesterol

| PRJNA535515 | ENA

SREBP1c and mock virus expression profiles in AG01518 human fibroblasts

Project description:Sterol-regulatory element binding proteins (SREBP) control the expression of most genes involved in fatty acid and cholesterol metabolism. In this report, using microarrays, we showed that SREBP1 also induced genes unrelated to lipid biosynthesis, such as heme oxygenase 1 (HMOX1), the phosphatidylinositol-3 kinase regulatory subunit p55-gamma, synaptic vesicle glycoprotein 2A (SV2A) and COTE1 (C1orf2). These genes were regulated by infection with adenoviruses encoding active SREBP1, sterols, statins and growth factors, as one would expect from SREBP1 target genes Keywords: treatment comparaison

2007-04-26 | GSE6877 | GEO

Saturated fat diet induces transintestinal cholesterol excretion in mice

Project description:Intake and absorption of cholesterol (the latter determined by double labeled cholesterol methodology) were nearly unchanged in mice fed the saturated fat diet, but the fecal excretion of neutral sterols (i.e. cholesterol and its microbial conversion products) was increased compared with control diet(+80%; p<0.01). The saturated fat diet did neither significantly affect biliary cholesterol secretion nor intestinal cholesterol absorption (49% vs. 65% in controls, double labeled water methodology, p>0.1). Thus, the increased fecal neutral sterol excretion was primarily due to increased net transintestinal cholesterol excretion (+89% versus control; p<0.05). Since a major fraction of TICE cholesterol absorption is normally reabsorbed (J Lipid Res 2019 Sep;60(9):1562-1572), the increased fecal cholesterol excretion could be due to more transintestinal excretion of cholesterol into the intestinal lumen and/or to its decreased reabsorption. The saturated fat diet increased jejunal expression of genes involved in cholesterol synthesis (Srebf2 and target genes), but did not affect whole body de novo cholesterol synthesis. Conclusion This proof-of-principle study shows that increasing the saturation of the dietary fat can stimulate fecal cholesterol excretion. Individual components of saturated fat diets are to be explored to address the responsible molecular mechanisms

2021-02-01 | GSE37097 | GEO

Transcriptomic sterol response in the HepG2 human hepatoma cell line

Project description:Statins are cholesterol lowering drugs that inhibit cholesterol synthesis and reduce intracellular sterol levels, stimulating a transcriptional response. We sought to identify genes that were statin responsive in the HepG2 human hepatoma cell line and determine which of those genes were sterol responsive using sterol addback conditions. Though the vast majority of statin responsive genes are sterol responsive, we identified a subset of statin responsive genes whose gene expression changes are not reversed upon sterol addback.

2024-12-10 | GSE190736 | GEO

Zinc finger transcription factors displaced SREBP proteins as the major sterol regulators during Saccharomycotina evolution

Project description:All but a few eukaryotes die without oxygen and respond dynamically to changes in the level of oxygen available to them. One ancient oxygen-requiring biochemical pathway in eukaryotes is the pathway for the biosynthesis of sterols, leading to cholesterol in animals and ergosterol in fungi. Mutations in this pathway are a frequent cause of azole drug resistance in pathogenic fungi. The regulatory mechanism for the sterol pathway is also widely conserved between animals and fungi and is centred on a transcription activator, SREBP, that forms part of a sterol-sensing complex. However, in one group of yeasts – the Saccharomycotina, which includes the major pathogen Candida albicans – control of the sterol pathway has been taken over by an unrelated regulatory protein, Upc2. We show here by analysis of the yeast Yarrowia lipolytica that the evolutionary switch from SREBP to Upc2 was a two-step process in which Upc2 appeared in an ancestor of Saccharomycotina, and SREBP subsequently degenerated and lost its sterol-regulatory function while retaining an ancient role in filamentation.

2013-11-19 | GSE47433 | GEO

Zinc finger transcription factors displaced SREBP proteins as the major sterol regulators during Saccharomycotina evolution

Project description:All but a few eukaryotes die without oxygen and respond dynamically to changes in the level of oxygen available to them. One ancient oxygen-requiring biochemical pathway in eukaryotes is the pathway for the biosynthesis of sterols, leading to cholesterol in animals and ergosterol in fungi. Mutations in this pathway are a frequent cause of azole drug resistance in pathogenic fungi. The regulatory mechanism for the sterol pathway is also widely conserved between animals and fungi and is centred on a transcription activator, SREBP, that forms part of a sterol-sensing complex. However, in one group of yeasts M-bM-^@M-^S the Saccharomycotina, which includes the major pathogen Candida albicans M-bM-^@M-^S control of the sterol pathway has been taken over by an unrelated regulatory protein, Upc2. We show here by analysis of the yeast Yarrowia lipolytica that the evolutionary switch from SREBP to Upc2 was a two-step process in which Upc2 appeared in an ancestor of Saccharomycotina, and SREBP subsequently degenerated and lost its sterol-regulatory function while retaining an ancient role in filamentation. RNA was isolated from Y. lipolytica wildtype (JMY2900) in normoxia (21% oxygen, 4 biological replicates), wildtype (JMY2900) in hypoxia (1% oxygen, 5 biological replicates), upc2 deletion (SMY2) in hypoxia (1% oxygen, 3 biological replicates), and from sre1 (SMY5, SMY8) deletion in hypoxia (1% oxygen, 2 biological replicates). Gene expression was determined using strand-specific RNA-seq.

2013-11-19 | E-GEOD-47433 | biostudies-arrayexpress

A PhotoClick cholesterol-based quantitative proteomics screen for cytoplasmic sterol binding proteins in Saccharomyces cerevisiae

Project description:Ergosterol is a prominent component of the yeast plasma membrane and essential for yeast cell viability. It is synthesized in the endoplasmic reticulum and transported to the plasma membrane by non-vesicular mechanisms requiring carrier proteins. Oxysterol binding protein homologues and yeast StARkin proteins have been proposed to function as sterol carriers. Although many of these proteins are capable of transporting sterols between synthetic lipid vesicles in vitro, they are not essential for ergosterol transport in cells, indicating that they may be functionally redundant with each other or with additional - as yet unidentified - sterol carriers. To address this point we hypothesized that sterol transport proteins are also sterol binding proteins (SBPs), and used an in vitro chemo-proteomic strategy to identify all cytosolic SBPs. We generated a cytosol fraction enriched in SBPs and captured the proteins with a photoreactive clickable cholesterol analog. Quantitative proteomics of the captured proteins identified 342 putative SBPs. Analysis of these identified proteins based on their annotated function, reported drug phenotypes, interactions with proteins regulating lipid metabolism, gene ontology, and presence of mammalian orthologs revealed a subset of 62 characterized and nine uncharacterized candidates. Five of the uncharacterized proteins play a role in maintaining plasma membrane integrity as their absence affects the ability of cells to grow in the presence of nystatin or myriocin. We anticipate that the dataset reported here will be a comprehensive resource for functional analysis of sterol binding/transport proteins and provide insights into novel aspects of non-vesicular sterol trafficking.

2019-11-25 | PXD014555 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data