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NAD+ and PPAR-modifying drugs in a C. elegans model of respiratory chain complex I deficiency

ABSTRACT: The gas-1(fc21) mutation affects the 49 kD subunit of complex I, decreasing the rate of complex I-dependent oxidative phosphorylation. This is a model for human mitochondrial respiratory chain disease. NAD+ and PPAR-modifying drugs may confer benefits with respect to lifespan in these short-lived mutant worms. Analysis of gas-1(fc21) electron transport chain complex I mutants treated either starting in development or in young adulthood only with nicotinic acid (1 mM), resveratrol (50 microM), rosiglitazone (5 mM) or fenofibrate (14 microM) is presented. The goal is to detect transcriptional changes in clusters of genes using gene set enrichment analysis to explain treament effects in these mutant worms.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE57626 | GEO | 2014/08/13

SECONDARY ACCESSION(S): PRJNA247360

REPOSITORIES: GEO

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NAD+ and PPAR-modifying drugs in a C. elegans model of respiratory chain complex I deficiency

Project description:The gas-1(fc21) mutation affects the 49 kD subunit of complex I, decreasing the rate of complex I-dependent oxidative phosphorylation. This is a model for human mitochondrial respiratory chain disease. NAD+ and PPAR-modifying drugs may confer benefits with respect to lifespan in these short-lived mutant worms. Analysis of gas-1(fc21) electron transport chain complex I mutants treated either starting in development or in young adulthood only with nicotinic acid (1 mM), resveratrol (50 microM), rosiglitazone (5 mM) or fenofibrate (14 microM) is presented. The goal is to detect transcriptional changes in clusters of genes using gene set enrichment analysis to explain treament effects in these mutant worms. Four biological replicates were performed for each treatment condition (nicotinic acid, resveratrol, rosiglitazone, and fenofibrate) for each drug beginning either in development or in young adulthood for gas-1 mutant worms, i.e., 8 treated samples in total. At most one outlier was excluded from each analysis. Untreated N2 and gas-1 in each of the control solvents (S-basal, for nicotinic acid, and 1% DMSO, for resveratrol, rosiglitazone, and fenofibrate) were also analyzed; at least 3 replicates of each were included. These were used as sources of total RNA, each for hybridization to a single Affymetrix whole-genome microarray. Analysis was performed to reveal transcriptional changes related to mutantion and/or drug treatment effects.

2014-08-13 | E-GEOD-57626 | biostudies-arrayexpress

Expression data from the complex I mutant gas-1 (fc21) C. elegans worms in comparison to wildtype N2 Bristol worm and under the inluence combination drug therapy

Project description:We studied genome-wide expression profiles of C. elegans young adult worms, complex I mutant gas-1(fc21) compare to the wild type N2 Bristol worm and the effect of combination drug treatment on the gene expression profile in gas-1(fc21).

2021-07-01 | GSE134535 | GEO

Expression data from the complex I mutant gas-1 (fc21) C. elegans worms in comparison to wildtype N2 Bristol worm and under the inluence of antioxidant drug treatment

Project description:We studied genome-wide expression profiles of C. elegans young adult worms, complex I mutant gas-1(fc21) compare to the wild type N2 Bristol worm and the effect of different antioxidant drug treatment on the gene expression profile in gas-1(fc21).

2017-03-01 | GSE66680 | GEO

CEST-2.2 stimulates lipid metabolism and promotes longevity in mitochondrial mutant animals (RNA-Seq)

Project description:Intestine-specific transcriptome of wild-type. gas-1(fc21) and gas-1(fc21); cest-2.2 OE Caenorhaditis elegans in order to gain insight into how cest-2.2 overexpression ameliorates Complex I deficiency

2021-10-01 | GSE168501 | GEO

Transcriptome of a long-lived mutant nematode with severe mitochondrial deficiency

Project description:Inhibition of insulin/IGF-1 signaling (IIS) represents a promising avenue for the treatment of mitochondrial diseases, although many of the molecular mechanisms underlying this beneficial effect remain elusive. Here, we analyze the transcriptome of a well established model for mitochondrial deficiency, gas-1(fc21) mutant nematodes, which when placed in a genetic context of IIS inhibition, undergo metabolic rewiring leading to a massive lifespan extension

2019-02-12 | GSE122902 | GEO

Expression data from the complex I mutant gas-1 (fc21) C. elegans worms in comparison to wildtype N2 Bristol worm and under the inluence combination drug therapy

Project description:Expression data from the complex I mutant gas-1 (fc21) C. elegans worms in comparison to wildtype N2 Bristol worm and under the inluence combination drug therapy

| PRJNA556493 | ENA

Caenorhabditis elegans

Project description:Expression data from the complex I mutant gas-1 (fc21) C. elegans worms in comparison to wildtype N2 Bristol worm and under the inluence of antioxidant drug treatment

| PRJNA277719 | ENA

Endothelial cells and atorvastatin

Project description:Rationale: Immortalized cells may exhibit important differences relative to their primary cell counterparts. Microarrays were used compare primary human umbilical vein endothelial cells (HUVECs) and the immortalized HUVEC cell line EA.hy926, in their response to inhibition of the mevalonate pathway by a HMG-CoA reductase inhibitor (atorvastatin). The effects of atorvastatin were reversed by the addition of mevalonate, to subtract non-specific changes in gene expression. Methods: Confluent cell cultures of HUVECs and EA.hy926 cells (two independent experiments in each cell type) were incubated with 1) statin-free media; 2) 10 microM atorvastatin; 3) 500 microM mevalonate; or 4) a combination of 10 microM atorvastatin and 500 microM mevalonate. All cells were harvested at 24 h. Total RNA was isolated using Trizol reagent (Invitrogen). cDNA was prepared from 10 microgram total RNA using a double-stranded cDNA synthesis kit (Life Technologies) with a T7-dT24 primer for first-strand synthesis. cRNA was synthesized from cDNA and biotinylated using the BioArray High Yield RNA Transcript Labeling Kit (Enzo Diagnostics). Twenty microgram of cRNA was fragmented by heating at 94°C for 35 min in fragmentation buffer, containing 40 mM Tris-acetate, pH 8.1, 125 mM KOAc, 30 mM MgOAc. Fifteen micrgram of fragmented cRNA, together with control cRNAs and grid alignment oligonucleotides, were hybridized overnight to GeneChip Human Genome U133A 2.0 arrays (Affymetrix) at 45°C under constant rotation. Arrays were washed and incubated with an anti-streptavidin antibody. Fluorescent signals were measured using an Agilent Gene Array Laser Scanner and analyzed with MicroArray Suite 5.0 (Affymetrix). Microarrays were scaled using default settings. Keywords: other

2005-03-29 | GSE2450 | GEO

Nitrogen gas supply to lactate-based chain elongation

Project description:Nitrogen gas supply to lactate-based chain elongation

| PRJEB43372 | ENA

Synechocystis PCC6803 dose responses to iron starvation (96h).

Project description:The transcriptome approach was used to characterize the global change (2 Fe concentrations) in Synechocystis gene expression in response to continuous iron starvation, compared to standard medium (17 microM). For iron depletion, exponentially growing cells were washed in Fe-free medium, and grown for 48 hrs under standard conditions in liquid medium cotaining either 1 mM or 2 mM of ferric ammonium citrate. Then, cells were washed, and resuspended in Fe-free medium (Fe contaminations 0.5 microM) and grown for another 48 hrs period. For each concentration point, total RNA were isolated from stressed and unstressed cells, reverse-transcribed, differentially labelled (dye swapped), hybridized together (stressed versus unstressed samples) and analyzed with DNA glass microarrays (two slides per each concentration point) (Custom-commercial array : IntelliGeneTM CyanoCHIP version 2.0, TAKARA). To identify differentially expressed genes, the median of the normalized ratio of Cy5/Cy3 intensity was calculated for each spot of the replicated dye-swap. The results of the analysis were carefully examined to exclude the dye effect between the 2 Cy-swapped arrays. Keywords: stress responses

2005-12-07 | GSE3717 | GEO

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