ApoD modulation mouse cerebellar transcriptome
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE28643 | GEO | 2011/04/16
SECONDARY ACCESSION(S): PRJNA138953
REPOSITORIES: GEO
Similar Datasets
Project description:The lipocalin Apolipoprotein D (ApoD), known to protect the nervous system against oxidative stress (OS) in model organisms, is up-regulated early in the mouse brain in response to the ROS generator paraquat (PQ). However, the processes triggered by this up-regulation have not been explored. We present here a study of the effect of ApoD on the early transcriptional changes upon OS in the mouse cerebellum using microarray profiling. ApoD-KO and transgenic mice over-expressing ApoD in neurons are compared to wild-type controls.
2011-04-16 | E-GEOD-28643 | biostudies-arrayexpress
Project description:Oxidative stress (OS) results from genetic defects or stressful environmental challenges that cause unchecked production of reactive oxygen species (ROS). OS has been implicated in many diseases due to its wide ranging damage to nucleic acids, proteins and lipids. Using Halobacterium salinarum NRC-1, an extremophile that thrives under conditions of excessive OS, we have constructed a systems model for oxidative stress response (OSR) by integrating transcriptional changes induced by treatments with H2O2 and paraquat, functional associations inferred through comparative genomics, and de novo discovered cis-regulatory motifs. Together with phenotypic analysis of mutant strains this has revealed a multi-tiered OS management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids, and gas vesicles, metal trafficking, and various other aspects of metabolism. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was previously constructed from cellular responses to diverse environmental perturbations –this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of g rays. Mid-log phase cultures of H. salinarum NRC-1 (2 biological replicates) grown in flasks were treated with either sub-lethal concentrations of 25mM H2O2 or 4mM PQ and incubated with shaking for up to 240 min. For each treatment, two time courses were run to determine the transcriptional responses to (1) constant stress and (2) recovery of H. salinarum NRC-1 to H2O2 and PQ. During constant stress, culture aliquots (~4ml) were collected over a time course (-1, 5, 10, 20, 40, 80 and 160 minutes), centrifuged (16000g, 90 seconds) and flash frozen. For recovery, cells were first treated for 2-hours with either 25 mM H2O2 or 4mM PQ, recovered by centrifugation, washed and re-suspended in CM. Cultures were returned to the incubator with shaking and samples were taken at 0, 10, 20, 30, 40, 50, 60, 120, and 240 minutes and processed as described previously. Analysis of temporal transcriptional changes (-1, 0, 5, 10, 20, 40, 80, 160 and 320m) to sub-inhibitory concentrations of PQ (0.25mM) was also characterized. Total RNA was prepared and labeled with Alexa547 and Alexa647 dyes. Intensities were normalized between the Alexa 546 and Alexa 647 channels by scaling all intensities in one channel such that the 75th percentile in each channel was made equal.
2010-05-26 | E-GEOD-17515 | biostudies-arrayexpress
Project description:Biological aging is the dominant risk factor for most chronic diseases. Development of anti-aging interventions offers the promise of simultaneously preventing or even treating many chronic illnesses. Cellular stress resistance is an evolutionarily conserved feature of longevity. Here, we identify compounds that confer resistance to the superoxide generator paraquat (PQ), the heavy metal cadmium (Cd), and the DNA alkylator methyl methanesulfonate (MMS). Some rescue compounds conferred resistance to a single stressor, while others conferred multiplex stress resistance. Induction of stress resistance in mouse fibroblasts was highly predictive of longevity extension in a published large-scale longevity screen in C. elegans. Transcriptomic analysis implicated NRF2 signaling in stress resistance provided by two protective compounds, cardamonin and AEG 3482. Molecules that conferred resistance to PQ also induced cellular inflammatory pathways, and core pathways such as AMPK signaling. Following further optimization, small molecules identified in this work, particularly those that promote resistance to multiple distinct stressors, may represent attractive candidates to evaluate for potential pro-health and pro-longevity effects in mammals.
2020-10-02 | GSE130294 | GEO
Project description:We use RNAseq to compare the transcriptomes of wild type and cells treated with 2.5 mM paraquat (PQ) for 8 hr. We find that PQ treatment results in changes in the transcripts for hundreds of genes. A notable subset of PQ-induced transcripts encodes proteins activated by the retrograde response pathway. This pathway is activated by ETC dysfunction and regulates carbohydrate metabolism to increase synthesis of biosynthetic intermediates through pathways including the TCA cycle, glutamine biosynthetic pathway, and isocitrate metabolism. Transcripts encoding oxidative stress response proteins (e.g. amino acid and iron transporters and siderophores) are also more abundant in PQ-treated cells.
2020-05-19 | GSE150804 | GEO
Project description:We validated context dependent regulation by two FFRPs AsnC and VNG1237C by deleting the FFRP and testing the effect on downstream target genes. For validtion of AsnC condition specific regulation we grew wild-type and delta-AsnC in the presence of 4mM paraquat (PQ) and samples at 1 and 160 minutes post addition of this sub-lethal dose of PQ. For validation of VNG1237C we grew wild-type and delta-VNG1237C in a standard growth curve sampling at OD 0.18 and 1.15. The asnC deletion strain (M-bM-^HM-^FasnC) and the control M-bM-^HM-^Fura3 strain were grown in 4mM paraquat (PQ) and were sampled at 1 and 160 minutes after PQ addition. Sampling timing for M-bM-^HM-^FVNG1237C was designed such that the starting ODs were as similar as possible and once an OD of 1.17 was reached for M-bM-^HM-^Fura3 the M-bM-^HM-^FVNG1237C was sampled at this same time point.
2014-10-02 | E-GEOD-61975 | biostudies-arrayexpress
Project description:Despite its banishment in several countries, Paraquat (PQ) is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human or animal brain cells such as glial cells or neurons through biological processes as redox by generation of Reactive Oxygen Species (ROS). This specific perturbation has already proven its association for increasing the risk of developing a long-term brain impairment in in vitro and in vivo studies using brain cells. However, there is few evidence of PQ effect on Human Brain Microvascular Endothelial Cells (HBMECs), a particular cell type acting as a macromolecule permeability regulator in the Blood-Brain Barrier (BBB). The present study aimed at unraveling biological mechanisms associated to the exposition of 1, 10 and 100 µM of PQ for 24h on HBMECs. High-throughput mass spectrometry-based proteomics using data-independent acquisition (DIA) was applied. Biological pathway enrichment and cellular assays such as mitochondrial respiration and cholesterol level of PQ-treated HBMECs were performed to verify proteomics results. Proteomic experiment reported a total of 3753 quantified proteins out of which 419 were significantly modulated by paraquat exposure. Biological pathway enrichment revealed that the modified proteins are involved in pathways such as the ubiquinone metabolism, a pathway directly linked to mitochondrial complex I proteins. This study also unveiled the modulation of the cholesterol metabolism. In conclusion, most of the highly differentially expressed proteins (DEPs) in PQ-treated HBMECs were associated to the ubiquinone metabolism pathway confirming the well know mechanism of PQ inducing oxidative stress and inhibit mitochondrial complex I activity. Additionally, this study also described the cholesterol biosynthesis modulation on primary human brain endothelial cells not yet described.
2022-02-17 | PXD026975 | Pride
Project description:A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism. The brain cortex and hippocampus of young and aged mice of wild-type and ApoD-KO genotypes were used for RNA extraction and hybridization on Affymetrix microarrays. We aim at identifying distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus.
2015-04-23 | E-GEOD-68169 | biostudies-arrayexpress
Project description:PURPOSE: Pulmonary fibrosis (PF) is a pathological state presenting at the progressive stage of heterogeneous interstitial lung disease (ILD). The molecular mechanisms are incompletely understood. We built a mouse model of lung fibrosis induced by paraquat. Using transcriptome analysis, we identified differentially expressed proteins (DEGs) and provided further functional analysis. METHODS: We built a mouse model of lung fibrosis through intratracheal instillation of paraquat. After instillation, mice were kept for 7 and 28 days, respectively. we performed time-series RNA sequencing (RNA-Seq) on the lung samples from paraquat treated mice and saline control. The DEGs were verified by qPCR. RESULTS: The transcriptome data found a total of 1345 of differentially expressed genes (DEGs) up-regulated and 844 DEGs down-regulated significantly in paraquat group on day 7. There were 511 DEGs up-regulated and 179 DEGs down-regulated remarkably on day 28 after PQ instillation (Fold Change ≥2 and Q value ≤0.001). We verified 6 significantly changed genes by qPCR, proving the accuracy of RNA-seq. CONCLUTION: Our transcriptomic study assigns genes for fibrogenesis and reveals their dynamic changes from lung injury to repair, providing new insights for the and development of biomarkers and treatment in fibrotic diseases.
2024-04-01 | GSE171625 | GEO
Project description:A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism.
2015-04-23 | GSE68169 | GEO
Project description:We validated context dependent regulation by two FFRPs AsnC and VNG1237C by deleting the FFRP and testing the effect on downstream target genes. For validtion of AsnC condition specific regulation we grew wild-type and delta-AsnC in the presence of 4mM paraquat (PQ) and samples at 1 and 160 minutes post addition of this sub-lethal dose of PQ. For validation of VNG1237C we grew wild-type and delta-VNG1237C in a standard growth curve sampling at OD 0.18 and 1.15.
2014-10-02 | GSE61975 | GEO