Expression data from wild type C. elegans and 5 osmotic stress resistant mutants exposed to hyper/isotonic environments
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE19310 | GEO | 2009/12/04
SECONDARY ACCESSION(S): PRJNA120905
REPOSITORIES: GEO
Similar Datasets
Project description:Adaptation of C. elegans to hypertonic environments involves the accumulation of the organic osmolyte glycerol via transcriptional upregulation of the glycerol biosynthestic enzyme gpdh-1. A number of mutants, termed osmotic stress resistant (osr) mutants, have been identified. osr mutants cause constitutive upregulation of gpdh-1 and confer extreme resistance to hypertonicity. We tested the hypothesis that osr mutants broadly activate a gene expression program normally activated by osmotic stress in wild type animals using Affymterix microarray analysis of the hypertonic stress response in wild type animals and of constituitive gene expression changes in five osr mutants. Experiment Overall Design: Young adult C. elegans were exposed to hypertonic growth plates for varying times prior to RNA extraction and hybridization on Affymetrix microarrays. Since we wished to separate direct response from secondary responses to osmotic stress, we collected worms following short term exposures to hypertonic conditions (15 minutes and 1 hour) and after long term exposure to hypertonic conditions (6 hours or a full generation of growth under hypertonic conditions). We also collected young adults from the osr mutants osm-7, osm-8, osm-11, dpy-9, and dpy-10 for microarray analysis. These mutants were grown under isotonic conditions to determine whether that constitutively activate genes normally regulated by hypertonic stress in wild type animals.
2009-12-14 | E-GEOD-19310 | biostudies-arrayexpress
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation. Quadruplicate samples were collected for each condition and then pooled into a single sample for hybridization to microarrays.
2010-12-10 | E-GEOD-25816 | biostudies-arrayexpress
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
2010-12-10 | GSE25816 | GEO
Project description:Regulation of cell volume is essential for tissue homeostasis and cell viability. In response to hypertonic stress, cells need rapid electrolyte influx to compensate water loss and to prevent cell death in a process known as regulatory volume increase (RVI). However, the molecular component able to trigger such process was unknown to date. Using a genome wide CRISPR/Cas9 screen, we identified LRRC8A, which encodes a chloride channel subunit, as the gene most associated with cell survival under hypertonic conditions. Hypertonicity activates the p38 stress-activated protein kinase pathway and its downstream MSK1 kinase, which phosphorylates and activates LRRC8A. LRRC8A-mediated Cl efflux facilitates activation of the with-no-lysine (WNK) kinase pathway, which in turn, promotes electrolyte influx via Na+ /K+ /2Cl cotransporter (NKCC) and RVI under hypertonic stress. LRRC8A-S217A mutation impairs channel activation by MSK1, resulting in reduced RVI and cell survival. In summary, LRRC8A is key to bidirectional osmotic stress responses and cell survival under hypertonic conditions.
2021-05-29 | GSE158316 | GEO
Project description:Hypertonicity in renal medulla is essential for urine concentration and water homeostasis. However, how renal medullary collecting duct cells (MCDs) survive and function under the harsh hypertonic stress remains incompletely understood. By using the RNA-seq technique, we identified SNAT2 (slc38a2) as a novel osmoresponsive neutral amino acid transporter in MCD cells. We found that hypertonic stress induced cell death of MCDs mainly via ferroptosis.
2023-02-15 | GSE206476 | GEO
Project description:Protein function is controlled by the cellular proteostasis network. Proteostasis is energetically costly and those costs must be balanced with the energy needs of other physiological functions. Hypertonic stress causes widespread protein damage in C. elegans. Suppression and management of protein damage is essential for optimal survival under hypertonic conditions. ASH chemosensory neurons allow C. elegans to detect and avoid strongly hypertonic environments. We demonstrate that gene mutations that disrupt ASH mediated hypertonic avoidance behavior or genetic ablation of ASH neurons enhance survival during hypertonic stress. Enhanced survival is not due to altered systemic volume homeostasis or organic osmolyte accumulation. Instead, loss of ASH neuron function reduces protein damage in non-neuronal cells. Improved proteostasis capacity is due in part to upregulation of genes that play important roles in managing protein damage. We propose that inhibitory signaling from ASH neurons normally suppresses expression of genes required for non-neuronal cell proteostasis. Because all cells have the capacity to sense and respond to stressors, inhibitory neuronal signaling may be important for minimizing activation of cellular stress resistance and proteostasis pathways during short duration and less extreme stressors or stressors that can be avoided by behavioral changes. Neuronal regulation of systemic proteostasis allows the nervous system to monitor environmental variables and more effectively partition finite energy resources between different organismal processes. Our studies add to a growing body of work demonstrating that intercellular communication between neuronal and non-neuronal cells plays a critical role in integrating cellular stress resistance with other organismal physiological demands and associated energy costs. mRNA expression profiling of synchronized L4 stage wild-type N2 Bristol and VC1262 osm-9(ok1677) C. elegans strains under control (51mM NaCl) and hypertonic stress (200mM NaCl).
2016-06-01 | E-GEOD-73589 | biostudies-arrayexpress
Project description:Petelenz-kurdzeil2013 - Osmo adaptation
gpd1D
This model is described in the article:
Quantitative analysis of
glycerol accumulation, glycolysis and growth under hyper
osmotic stress.
Petelenz-Kurdziel E, Kuehn C,
Nordlander B, Klein D, Hong KK, Jacobson T, Dahl P, Schaber J,
Nielsen J, Hohmann S, Klipp E.
PLoS Comput. Biol. 2013; 9(6):
e1003084
Abstract:
We provide an integrated dynamic view on a eukaryotic
osmolyte system, linking signaling with regulation of gene
expression, metabolic control and growth. Adaptation to osmotic
changes enables cells to adjust cellular activity and turgor
pressure to an altered environment. The yeast Saccharomyces
cerevisiae adapts to hyperosmotic stress by activating the HOG
signaling cascade, which controls glycerol accumulation. The
Hog1 kinase stimulates transcription of genes encoding enzymes
required for glycerol production (Gpd1, Gpp2) and glycerol
import (Stl1) and activates a regulatory enzyme in glycolysis
(Pfk26/27). In addition, glycerol outflow is prevented by
closure of the Fps1 glycerol facilitator. In order to better
understand the contributions to glycerol accumulation of these
different mechanisms and how redox and energy metabolism as
well as biomass production are maintained under such conditions
we collected an extensive dataset. Over a period of 180 min
after hyperosmotic shock we monitored in wild type and
different mutant cells the concentrations of key metabolites
and proteins relevant for osmoadaptation. The dataset was used
to parameterize an ODE model that reproduces the generated data
very well. A detailed computational analysis using
time-dependent response coefficients showed that Pfk26/27
contributes to rerouting glycolytic flux towards lower
glycolysis. The transient growth arrest following hyperosmotic
shock further adds to redirecting almost all glycolytic flux
from biomass towards glycerol production. Osmoadaptation is
robust to loss of individual adaptation pathways because of the
existence and upregulation of alternative routes of glycerol
accumulation. For instance, the Stl1 glycerol importer
contributes to glycerol accumulation in a mutant with
diminished glycerol production capacity. In addition, our
observations suggest a role for trehalose accumulation in
osmoadaptation and that Hog1 probably directly contributes to
the regulation of the Fps1 glycerol facilitator. Taken
together, we elucidated how different metabolic adaptation
mechanisms cooperate and provide hypotheses for further
experimental studies.
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BIOMD0000000610.
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2016-04-20 | BIOMD0000000610 | BioModels
Project description:Protein function is controlled by the cellular proteostasis network. Proteostasis is energetically costly and those costs must be balanced with the energy needs of other physiological functions. Hypertonic stress causes widespread protein damage in C. elegans. Suppression and management of protein damage is essential for optimal survival under hypertonic conditions. ASH chemosensory neurons allow C. elegans to detect and avoid strongly hypertonic environments. We demonstrate that gene mutations that disrupt ASH mediated hypertonic avoidance behavior or genetic ablation of ASH neurons enhance survival during hypertonic stress. Enhanced survival is not due to altered systemic volume homeostasis or organic osmolyte accumulation. Instead, loss of ASH neuron function reduces protein damage in non-neuronal cells. Improved proteostasis capacity is due in part to upregulation of genes that play important roles in managing protein damage. We propose that inhibitory signaling from ASH neurons normally suppresses expression of genes required for non-neuronal cell proteostasis. Because all cells have the capacity to sense and respond to stressors, inhibitory neuronal signaling may be important for minimizing activation of cellular stress resistance and proteostasis pathways during short duration and less extreme stressors or stressors that can be avoided by behavioral changes. Neuronal regulation of systemic proteostasis allows the nervous system to monitor environmental variables and more effectively partition finite energy resources between different organismal processes. Our studies add to a growing body of work demonstrating that intercellular communication between neuronal and non-neuronal cells plays a critical role in integrating cellular stress resistance with other organismal physiological demands and associated energy costs.
2016-06-01 | GSE73589 | GEO
Project description:It is unclear how the amount of active nuclear MAPK over time quantitatively affects transcription. Here, we seek to address this issue by studying signal transduction and transcriptional response in a system that separates signalling from adaptation and hence signal strength from signal duration. The system is based on Saccharomyces cerevisiae osmoadaptation and allows modulation of the period of HOG-dependent responses without changing the initial stress intensity. The conditional osmotic stress system includes (i) a yeast mutant (gpd1 gpd2) unable to produce its main osmolyte glycerol, subsequently stressed with (ii) a stress inductor (polyols of different sizes) and allowed to adapt by (iii) expression of polyol flux-mediating aquaglyceroporin (rat AQP9). As there is no endogenous glycerol production, the osmoadaptation rate depends only on the size dependent equilibration rate over the plasma membrane of the polyol used as both stress inductor and compatible solute. Hence, we apply initially identical stresses but with differential durations, and determine the global transcriptional response.
2014-05-31 | GSE29716 | GEO
Project description:Stress adaptation is critical for the survival of microbes in dynamic environments, and in particular, for fungal pathogens to survive in and colonise host niches. Proteomic analyses have the potential to significantly enhance our understanding of these adaptive responses by providing insight into the post-transcriptional regulatory mechanisms that contribute to the outputs as well as testing presumptions about the regulation of protein levels based on transcript profiling. Therefore, in this study we used label-free, quantitative mass spectrometry to re-examine the response of the major fungal pathogen of humans, Candida albicans, to osmotic stress. Of the 1,262 proteins that were identified, 84 (7.7%) were reproducibly down-regulated in response to 1 M NaCl. These changes reflected the decrease in ribosome biogenesis and translation that often accompanies stress exposure. The 64 up-regulated proteins (5.1% of the total) included the glycerol biosynthetic enzymes, Gpd2 and Gpp1/Rhr2, as well as enzymes of central metabolism that may contribute to carbon flux to glycerol, a key osmolyte for this yeast. The up-regulated proteins also included proteins with functions during stress such as Hsp12, Hsp21, Cat1, Gsh2, Glx3 and Tps2, which was consistent with a perturbation of redox homeostasis and increased synthesis of the stress protectant trehalose during salt stress. These data reinforce the view that adaptation to salt stress involves a transient reduction in ribosome biogenesis and translation together with the accumulation of the osmolyte, glycerol. Given the small proportion of C. albicans proteins whose abundances are affected by salt stress, the results highlight the specificity of the metabolic response to salt stress.
2018-10-22 | PXD008362 | Pride