Transcriptome profile of S. cerevisiae treated with tauroursodeoxycholic acid (TUDCA)
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE186390 | GEO | 2024/11/13
REPOSITORIES: GEO
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Project description:We used dithiothreitol (DTT) and tauroursodeoxycholic acid (TUDCA) to induce or suppress ER stress in wheat cells, respectively, with the aim to reveal the molecular background of ER stress responses using miRNA sequencing. After sequencing, we revealed a total of 1,939 miRNAs involved in the process of ER stress response, including 1,740 known miRNAs and 199 novel miRNAs.
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Project description:We used dithiothreitol (DTT) and tauroursodeoxycholic acid (TUDCA) to induce or suppress ER stress in wheat cells, respectively, with the aim to reveal the molecular background of ER stress responses using degradome sequencing. After combined analysis of high-throughput sequencing, a total of 12,453 miRNA-target pairs were verified by degradome sequencing, and among them, 7,484 genes were targeted by 1,233 miRNAs.
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Project description:We used dithiothreitol (DTT) and tauroursodeoxycholic acid (TUDCA) to induce or suppress ER stress in wheat cells, respectively, with the aim to reveal the molecular background of ER stress responses using RNA sequencing. Transcriptomic analysis revealed that 8204 genes were differentially expressed in three treatment groups. Among these genes, 158 photosynthesis-related genes, 42 antioxidant enzyme genes, 318 plant hormone-related genes and 457 transcription factors (TFs) might play vital roles in regulating wheat response to ER stress.
2019-05-15 | GSE128485 | GEO
Project description:SEPN1 is a type II protein of the endoplasmic reticulum (ER) whose loss of function gives rise to a collection of debilitating autosomal recessive myopathies gathered under the umbrella term of SEPN1-related myopathy (RM). At the moment, SEPN1-RM lacks an effective pharmacological treatment; thus, the medical management of the disease is only supportive. The potentially fatal diaphragmatic weakness leading to respiratory insufficiency in patients still ambulant is the main reason for medical concerns. Thus, studies on SEPN1-RM pathogenesis are necessary to implement a targeted pharmacological therapy aimed at relieving the general muscle weakness and the more worrisome diaphragmatic dysfunction. Here, we show a physical and functional interaction between SEPN1 and the ER stress mediator ERO1 alpha (henceforth, ERO1). Both SEPN1 and ERO1 are involved in the redox regulation of proteins into the ER, although in an opposite way SEPN1 imposes a less oxidant ER poise while ERO1 a more oxidant one, conceivable with a reductase function of SEPN1 and an oxidase one of ERO1. Furthermore, both are mainly localized in a region of the ER in close contact with mitochondria termed mitochondria-associated membranes (MAMs) and their loss impacts oppositely on the short-range MAMs, thereby impinging ER-mitochondria Ca2+ dynamics, OXPHOS, and bioenergetics. We find that ERO1 depletion restores the impaired short-range MAMs due to SEPN1 loss together with mitochondrial ATP. ERO1 knockout in a mouse background of SEPN1 loss blunts ER stress and the consequent Unfolded Protein Response (UPR) while it rescues the diaphragmatic weakness by improving ER/mitochondria contacts, calcium dynamics, and OXPHOS. Importantly, treatments of SEPN1 knock out mice with the chemical chaperone tauroursodeoxycholic acid (TUDCA) mimic the results of ERO1 loss improving calcium dynamics, OXPHOS, ER/mitochondria contacts, thereby rescuing diaphragmatic weakness as well. In addition, TUDCA-treated SEPN1-RM patients-derived myoblasts show a dynamic dose-dependent increase in ATP levels under ER stress conditions suggesting improved mitochondrial function. Thus, our findings point to the ERO1 axis in the pathogenesis of SEPN1-RM thereby impinging on MAMs and mitochondria bioenergetics and recall for the efficacy of a pharmacology therapy with ad hoc ER stress/ERO1 inhibitors for SEPN1-RM.
2024-02-14 | E-MTAB-12460 | biostudies-arrayexpress
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Project description:Human B cells were isolated from peripheral blood from one healthy donor and two patients with Common Variable Immunodeficiency (CVID) and were immortalized by infection with Epstein Barr virus (EBV) in vitro. Immortalized EBV-B cells (in biological triplicates) were treated twelve different ways for 4 hours: 1.untreated control, 2. Thapsigargin (Tg) 1 µM, 3. Tunicamycin (Tm) 10 µg/ml, 4. 4-phenylbutyrate (4-PBA) 1 mM, 5. Tg 1 µM plus 4-PBA 1 mM, 6. Tm 10 µg/ml plus 4-PBA 1 mM, 7. Dimethyl sulfoxide (DMSO) 1 mM, 8. Tg 1 µM plus DMSO 1 mM, 9. Tm 10 µg/ml plus DMSO 1 mM, 10. Tauroursodeoxycholic acid (TUDCA) 5 mM, 11. Tg 1 µM plus TUDCA 5 mM, and 12. Tm 10 µg/ml plus TUDCA 5 mM. We used Applied Biosystems TaqMan OpenArray Real-Time PCR System (Thermo Scientific) to quantitate gene expression of relevant genes from the cells (in technical triplicates).
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Project description:Cholesterol efflux capacity dysfunction in macrophages is thought to be important in atherosclerosis. However, the molecular mechanism underlying this dysfunction remains unclear. Our previous analysis found that the increase of endoplasmic reticulum stress in macrophages during atherosclerotic plaque formation. Here we extended our analysis to ApoE-/- mice fed a high fat diet, some of which were treated with tauroursodeoxycholic acid (TUDCA) and collected the arteries of mice among these three groups (NFD, HFD and HFD+TUDCA) to perform the Bulk-RNA sequencing. There was significantly high expression of matrix metalloproteinase family (MMP9, MMP25, MMP8, MMP12, MMP13 and MMP3), CD68, inflammasome (IL1b, IL18bp, ifi44, ifi204 and Nlrp3), ER stress (Hspa5) and cholesterol transporters (ABCA1 and ABCG1) in the HFD group compared with the NFD group, however, TUDCA rescued the high expression of the above DEGs to different degrees. As shown by the expression levels of ifi204, Nlrp3, Il1b, and Il18, inflammasome activation was evident in the arteries of the HFD group compared to the NFD group. The ER stress inhibitor TUDCA not only decreased expression of the ER stress-related gene Hspa5 but also down-regulated inflammasome activation (as seen with the expression levels of ifi204, ifi44, NLRP3 and IL1b) in the artery of TUDCA treated mice compared with mice without drugs.
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Project description:The unfolded protein response (UPR) couples cellular translation rates and gene expression to the protein folding status of the endoplasmic reticulum (ER). Upon activation, the UPR machinery elicits a general suppression of protein synthesis and activation of stress gene expression, which act coordinately to restore protein folding homeostasis. We report here that UPR activation promotes the release of signal sequence-encoding mRNAs from the ER to the cytosol as a mechanism to decrease protein influx into the ER. This release of mRNA begins rapidly, then gradually recovers with ongoing stress. Upon release into the cytosol, these mRNAs have divergent fates: some synthesize full-length proteins, while others are translationally inactive and retain nascent protein chains. Together, these findings identify the dynamic subcellular localization of mRNAs and translation as a regulatory feature of the cellular response to protein folding stress. Cells were treated with a timecourse of Thapsigargin or DTT, then fractionated and analyzed by mRNA-seq or ribosome profiling
2014-08-28 | E-GEOD-53743 | biostudies-arrayexpress
Project description:The Unfolded Protein Response (UPR) is an adaptive pathway that restores cellular homeostasis after endoplasmic reticulum (ER) stress caused by an impairment of its protein folding capacity. The ER-resident kinase/ribonuclease Ire1 is the only UPR sensor that has been conserved during evolution from yeast to mammals; in these organisms, Ire1 transmits information from the ER to the nucleus trough the non-conventional splicing of Hac1 (yeast)/Xbp1 (metazoans) mRNA. We described the Dictyostelium discoideum ER-stress response and characterized its single bonafide Ire1 orthologue, IreA. We found that tunicamycin (TN) triggers a gene-expression program that increases the protein folding capacity of the ER and that alleviates ER protein load. Further, IreA resulted essential not only for cell-survival after TN-induced ER-stress, but also to accomplish about nearly 40% of the transcriptional changes induced upon a TN treatment. In addition, we described that autophagy is activated in Dictyostelium cells after a TN treatment and that autophagy-defective mutants exhibited increased sensitivity to this drug. The response of Dictyostelium cells to ER-stress involves the combined activation of an IreA-dependent gene expression program and the autophagy pathway.
2018-04-28 | GSE104409 | GEO
Project description:Erguler2013 - Unfolded protein stress response
The model investigates the mechanism by which UPR (unfolded protein response) outcome switches between survival and death.
This model is described in the article:
A mathematical model of the unfolded protein stress response reveals the decision mechanism for recovery, adaptation and apoptosis.
Erguler K, Pieri M, Deltas C.
BMC Syst Biol. 2013 Feb 21;7(1):16.
Abstract:
BACKGROUND: The unfolded protein response (UPR) is a major signalling cascade acting in the quality control ofprotein folding in the endoplasmic reticulum (ER). The cascade is known to play an accessory rolein a range of genetic and environmental disorders including neurodegenerative and cardiovasculardiseases, diabetes and kidney diseases. The three major receptors of the ER stress involved withthe UPR, i.e. IRE1a, PERK and ATF6, signal through a complex web of pathways to convey anappropriate response. The emerging behaviour ranges from adaptive to maladaptive depending on theseverity of unfolded protein accumulation in the ER; however, the decision mechanism for the switchand its timing have so far been poorly understood.
RESULTS:
Here, we propose a mechanism by which the UPR outcome switches between survival and death.We compose a mathematical model integrating the three signalling branches, and perform a comprehensivebifurcation analysis to investigate possible responses to stimuli. The analysis reveals threedistinct states of behaviour, low, high and intermediate activity, associated with stress adaptation, tolerance,and the initiation of apoptosis. The decision to adapt or destruct can, therefore, be understoodas a dynamic process where the balance between the stress and the folding capacity of the ER playsa pivotal role in managing the delivery of the most appropriate response. The model demonstratesfor the first time that the UPR is capable of generating oscillations in translation attenuation and theapoptotic signals, and this is supplemented with a Bayesian sensitivity analysis identifying a set ofparameters controlling this behaviour.
CONCLUSIONS:
This work contributes largely to the understanding of one of the most ubiquitous signalling pathwaysinvolved in protein folding quality control in the metazoan ER. The insights gained have direct consequenceson the management of many UPR-related diseases, revealing, in addition, an extended listof candidate disease modifiers. Demonstration of stress adaptation sheds light to how preconditioningmight be beneficial in manifesting the UPR outcome to prevent untimely apoptosis, and paves the wayto novel approaches for the treatment of many UPR-related conditions.
In the paper, PERKA refers to the amount of phosphorylated PERK monomer. However, it refers to the active complex in the model. The complex with the model parameterization is formed of 4 monomers (n=4). So, the value of PERKA should be multiplied by 4, in order to generate the figures in the paper (eg. Figure 12).
An additional parameter (tmr=10)) is used in the model. This parameter is not mentioned in the paper. The model values of kf(=10) and kr(=1) are not consistent with that of the paper (kf=100, kr=10, in the paper). However, this is corrected by the introduction of "tmr" in the model, which is multiplied with kf and kr to get the resulting values.
The term "tmr" was missing in the kinetic laws of the reactions reu7 and reu8, in the original model. This has been corrected as per the author's request.
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2024-09-02 | BIOMD0000000446 | BioModels