RNA-seq of human fibroblasts during normal aging and during aging with rotenone perturbation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: JenAge Project
PROVIDER: E-GEOD-64553 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Human fibroblasts at different population doublings were treated with low amounts of rotenone (mild stress) and compared to untreated fibroblasts. Two different cell lines were used (MRC-5, HFF). Illumina sequencing (HiSeq2000) was applied to generate 50bp single-end reads. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
2015-08-26 | GSE64553 | GEO
Project description:Quiescent MRC-5 fibroblasts were compared to young fibroblasts 6 samples: 3 biological replicates for each age group: young and quiescent MRC-5 cells. 50bp, single-end reads, no strand-specific reads
2014-11-06 | E-GEOD-60883 | biostudies-arrayexpress
Project description:Background: We here show that inhibitors of mitochondrial complex I promote physical activity, stress resistance as well as lifespan of Caenorhabditis elegans despite normal food uptake, i.e. in the absence of DR. Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. The RNA-seq data comprises 4 age groups (1, 5, 10 and 20 days after L4) and 2 different conditions (rotenone and normal feeding (DMSO)) 22 samples: mRNA profiles of 1-day, 5-day and 10-day old worms as triplicates for each, rotenone and solvent control treatment; mRNA profiles of 20-day old worms as duplicates for each, rotenone and solvent control treatment
2013-04-16 | E-GEOD-46051 | biostudies-arrayexpress
Project description:D-Glucosamine (2-amino-2-deoxy-D-glucose, C.A.S.# 3416-24-8) (GlcN) is a freely available and commonly used dietary supplement possibly promoting cartilage health in humans which also acts as an inhibitor of glycolysis. We here find that GlcN extends C. elegans lifespan by impairing glucose metabolism to activate AMP-activated protein kinase (AMPK/AAK2) leading to increased mitochondrial biogenesis. Consistent with the concept of mitohormesis, this promotes increased formation of mitochondrial reactive oxygen species (ROS) and p38/PMK-1-mediated stress signaling culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene. Ameliorating mitochondrial ROS formation as well as impairment of aat-1-expression abolishes GlcN-mediated lifespan extension in a NRF2/SKN-1-dependent fashion. Notably and unlike other calorie restriction mimetics (CRM) like 2-deoxy-D-glucose (2DG, DOG), GlcN extends lifespan of aging C57BL/6 mice (log-rank: p=0.002; cox regression: p=0.01) similarly paralleled by an induction of mitochondrial biogenesis, increased expression of several murine amino acid transporters, as well as increased amino-acid catabolism. Taken together, GlcN mimics a ketogenic diet to extend healthspan in evolutionary distinct species. 24 samples: 12 mRNA profiles of C.elegans: 6 without GlcN and 6 with GlcN supplementaion; 12 mRNA profiles of M.musculus: 6 without GlcN and 6 with GlcN supplementaion
2014-03-07 | E-GEOD-54853 | biostudies-arrayexpress
Project description:Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan of different species. Contrasting recent observations, we here find that overexpression of sir-2.1, the orthologue of mammalian SirT1, does extend C. elegans lifespan. Sirtuins are known to convert NAD+ into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, also in the absence of sir-2.1. Consistently, impairment of sir-2.1 prevents extension of lifespan by nicotinic acid (NA), a NAD+ precursor. Taken together, sirtuins extend lifespan by promoting formation of MNA to generate a phase I - mediated ROS signal, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation. 9 samples: 3 mRNA profiles of C.elegans 48h after L4 exposed to nicotinic acid; 3 mRNA profiles of C.elegans 48h after L4 exposed to 1-MNA; 3 mRNA profiles of C.elegans 48h after L4 as controls (H20)
2013-08-09 | E-GEOD-49662 | biostudies-arrayexpress
Project description:The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs. SK-N-MC cells were grown in three different conditions: media + vehicle (EtOH), media + a sublethal dose (5 nM) of rotenone, and media + a slightly toxic dose (50 nM) of rotenone. Gene expression was examined at 1 and 4 weeks of rotenone treatment. Three experiments were performed, each lasting 1 and 4 weeks. For each experiment, 5 separate dishes of vehicle-treated, and rotenone-treated cells were harvested at 1 and 4 weeks (30 independent samples at each time point) and pooled into 3 samples (vehicle treated,and rotenone treated with 5 nM and 50 nM) at each time point for a total of 18 individual samples from all thre experiments. Total RNA isolated from each of the 18 individual samples was used to prepared labeled cRNA and hybridized to one Genechip (Affymetrix) Human Genome array HG-U133A at the UCLA microarray core facility (http://microarray.genetics.ucla.edu/). After QC check, the data was normalized and used to assess expression indexes and fold changes (FC > 2.0, compared to vehicle-treated controls) using the model-based expression indexes (MBEI) method implemented in dCHIP, ( http://biosun1.harvard.edu/complab/dchip/), and the Signifiance Analysis of Microarrays (SAM) software for multiple test corrections. Enrichment analysis was performed by the functional annotation tools implemented in DAVID ( http://david.abcc.ncifcrf.gov), to ascertain sets of rotenone DRGs that are enriched in certain biological annotations.
2012-08-08 | E-GEOD-35642 | biostudies-arrayexpress
Project description:Adult male Sprague Dawley rats (5 month-old at the beginning of the study) were subcutaneously exposed to 0.5 mg.kg/d rotenone or the corresponding solvent (PEG/DMSO, 1/1) for 28 days. At the end of the experiment, animals were sacrificed by decapitation and brains were rapidly taken out within 30-40 s. Total RNA was prepared from laser-capture microdissected rat substantia nigra pars compacta (Snpc). Changes in transcript abundance within SNpc were analyzed on samples from solvent and rotenone-exposed groups (n = 3 per group) using CodeLink⢠Rat Whole Genome bioarrays containing 34,000 transcripts and EST probes (GE Healthcare, Amersham, Saclay, France). Two groups of rats were exposed either to rotenone (CR rats) or to solvents (CS rats) in order to analyse pesticides impact on gene expression.
2015-12-31 | E-GEOD-22364 | biostudies-arrayexpress
Project description:We designed a TMT peptide labeling-based quantitative proteomics strategy to achieve a high-accuracy analysis of proteomic changes in response to ER stress and mitochondria stress on INS-1 cells under three different culture conditions: control (Cont), rotenone (Rot), and thapsigargin (Tpg), each with five biological replicates. The TMT data was validated using label-free quantification method.
2023-07-20 | PXD030711 | Pride
Project description:We aimed to explore the neuroprotective efficacy of Yashtimadhu powder, prepared from the roots of Glycyrrhiza glabra L. (https://mpns.science.kew.org; http://www.ayurveda.hu/api/API-Vol-1.pdf) commonly known as licorice, a known Medhya rasayana in the Indian Ayurvedic texts against Parkinson’s disease. To test the efficacy of Yashtimadhu powder, we used rotenone to generate an in vitro PD model using retinoic acid-differentiated IMR32 cells. Yashtimadhu powder (Lot No.64) was procured from SDP Remedies and Research Centre, Mangalore, India, a GMP-certified Ayurvedic product manufacturer ((http://sdpayurveda.com/products/choorna/yastimadhu-choorna/)The Yashtimadhu neuroprotection was ascertained using cell cytotoxicity, activation of apoptotic proteins and kinases. We used Tandem mass tag (TMT)-lables to understand the differentially regulated proteins across various treatment groups, using Orbitrap Fusion Tribrid mass spectrometer. The mass spectrometry data is acquired in biological duplicates and technical triplicates. We report 4,864 proteins corresponding to 4,783 gene symbols. The proteins were filtered out based technical and biological replicate concordance, thereby reporting 3,720 proteins common among the biological replicates.
2021-09-09 | PXD019672 | Pride
Project description:Rotenone is a naturally occurring toxic substance from the Leguminosa plant and belongs to the group of compounds known as rotenoids (Bové et al., 2005). It is commercially used as a pesticide and is epidemiologically linked to PD. Being lipophilic, rotenone can diffuse across biological membranes in the body and gain entry to all the organs and cells (Bové et al., 2005). Rotenone can bind to complex I of the electron transport chain (ETC) and inhibit the enzymatic activity of the NADH-ubiquinone reductase (Schuler and Casida, 2001). This interferes with the oxidation phosphorylation process, and eventually causes cell damage via oxidative stress. Rotenone may also cause the depolymerisation of microtubules into tubulin monomers (Marshall and Himes, 1978). Accumulation of tubulin monomers is potentially cytotoxic, and it is believed that parkin reverses cytotoxicity by ubiquitinating these monomers and targeting them for proteasome degradation (Ren et al., 2003.). Unfortunately, in PD patients with parkin mutations, this is not possible and tubulin accumulates to harmful levels in the cells. A total of 13 RNA samples were analyzed. Cultured murine primary cortical neurons were treated with 10nM rotenone over a time-course of 8h, 15h and 24h (n=3) in addition to the vehicle control (n=4).
2013-12-31 | E-GEOD-22997 | biostudies-arrayexpress