Polyol stress: time course
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE29716 | GEO | 2014/05/31
SECONDARY ACCESSION(S): PRJNA141089
REPOSITORIES: GEO
Similar Datasets
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. Saccharomyces cerevisiae W303-1A (MATa leu2-3/112 ura3-1 trp1-1 his3-11/15 gpd1::TRP1 gpd2::URA3) osmotically stressed with 1M of glycerol, erythritol, xylitol or sorbitol. Samples are taken in triplicates (except for sorbitol 20 an 90 min and 20 min xylitol were duplicates were taken) in time course series after stress application. Total of 45 samples. RNA from from cultures of gpd1 gpd2 cells expressing rAQP9 prior to polyol exposure was used as reference RNA for all microarrays.
2014-05-31 | E-GEOD-29716 | biostudies-arrayexpress
Project description:Jörg Schaber & Edda Klipp. Short-term volume and turgor regulation in yeast. Essays in Biochemistry 45 (2008).
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.
2024-09-02 | BIOMD0000000607 | BioModels
Project description:Jörg Schaber & Edda Klipp. Short-term volume and turgor regulation in yeast. Essays in Biochemistry 45 (2008).
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.
2024-09-02 | BIOMD0000000606 | BioModels
Project description:Jörg Schaber & Edda Klipp. Short-term volume and turgor regulation in yeast. Essays in Biochemistry 45 (2008).
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.
2024-09-02 | BIOMD0000000603 | BioModels
Project description:Jörg Schaber & Edda Klipp. Short-term volume and turgor regulation in yeast. Essays in Biochemistry 45 (2008).
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.
2024-09-02 | BIOMD0000000604 | BioModels
Project description:Jörg Schaber & Edda Klipp. Short-term volume and turgor regulation in yeast. Essays in Biochemistry 45 (2008).
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.
2024-09-02 | BIOMD0000000605 | BioModels
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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2024-09-02 | BIOMD0000000610 | BioModels
Project description:The euryhaline marine yeast Debaromyces hansenii is a model system for the study of genes related to osmotic stress. To study the transcriptional response of this organism to osmotic stress we have used the two color microarray based gene expression analysis of 6211 genes which constitutes the whole genome. Analysis was done at three time points after induction with salt (0.5h, 3h and 6h.) The mRNA level of 64 genes significantly increased at least 3-fold after induction with 2M NaCl whereas that of 45 genes was 3-fold diminished. The induced as well as the repressed genes were grouped into functional categories to identify biochemical processes possibly affected by osmotic shock. 53% of the induced genes encode for ribosomal proteins, 12.5% for mitochondrial and redox, 6% for aminoacid, cell wall and carbohydrate, and 1.5%for heat shock, protein transport and glycerol proteins. The function of 31% of repressed genes is currently unknown. 15% of the repressed genes are involved in carbohydrate metabolism and protective function, 6% are associated with cell wall, redox and signal transduction, and 4% in vacuolar and lipid functions. Surprisingly, the activity of NAD+ glycerol 3-phosphate dehydrogenase gene (GPD1) involved in the glycerol biosynthesis in response to osmotic stress did not show induction. Keywords: time course, stress response, mRNA expression
2008-03-15 | GSE9911 | GEO
Project description:Glucose metabolism has been studied extensively, but the role of glucose-derived excretory glycerol remains unclear. Here, we show that hypoxia induces NADH accumulation to promote glycerol excretion and this pathway consumes NADH continuously, thus attenuating its accumulation and reductive stress. Aldolase B (ALDOB) accounts for glycerol biosynthesis by forming a complex with glycerol-3-phosphate dehydrogenases, GPD1 and GPD1L. Blocking GPD1, GPD1L, or glycerol 3-phosphate phosphatase exacerbates reductive stress and suppresses cell proliferation under hypoxia and tumor growth in vivo. Over-expression of these enzymes increases glycerol excretion but still reduces cell viability under hypoxia and tumor proliferation due to energy stress. AMPK inactivates ALDOB to mitigate glycerol synthesis that dissipates ATP, alleviating NADH accumulation-induced energy crisis. Therefore, glycerol biosynthesis/excretion regulates the trade-off between reductive stress and energy stress. Moreover, this mode of regulation seems to be prevalent in reductive stress-driven transformations, enhancing our understanding of the metabolic complexity and guiding tumor treatment.
2024-09-29 | PXD056351 |
Project description:Cancer stem cells (CSCs) are attractive targets for cancer therapy, however, little is known about how to target CSCs without affecting the normal stem cell population. Here we report the ribosome-profiling analysis of mouse neural stem cells and brain tumour stem cells (BTSCs), which leads to the identification of glycerol-3-phosphate dehydrogenase 1 (GPD1) as a CSC- specific determinant. We confirmed that GPD1 is expressed in BTSCs but not in neural stem cells. Intriguingly, expression of GPD1 is only found in the infiltrating dormant BTSCs in vivo and these cells start to divide and drive tumour relapse after chemotherapy. Most importantly, inhibition of GPD1 expression in tumour-bearing mice leads to prolonged survival. Further analysis shows that loss of GPD1 results in widespread changes in important pathways affecting BTSC maintenance. Human patient data analysis suggests that GPD1 is expressed in the dormant infiltrating tumour cells in human glioblastoma and the expression level is associated with a worse prognosis. This study provides an attractive therapeutic target for treating brain tumours and a novel aspect of regulation of CSC dormancy.
2019-07-15 | GSE110866 | GEO