CAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
SUBMITTER: Campbell Gourlay
PROVIDER: E-GEOD-25541 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This data provides evidence that elevation of cAMP levels has a dramatic effect on the transcriptome of yeast cells, with particular emphasis on mitochondrial function and the promotion of ROS production
2010-11-24 | GSE25541 | GEO
Project description:Protein kinase A (PKA), the main effector of second messenger cAMP, is highly conserved among eukaryotes and a paradigm for the mechanisms of regulation of protein kinases by ligands. The unique PKA holoenzymes in the phylogenetically distant protozoan parasite Trypanosoma are unresponsive to cAMP in vitro and in vivo. By small molecule screening and optimization, we designed direct, membrane-permeable activators binding with a kD of 9 nM to the CNB pockets of the T. brucei regulatory PKA subunit. 7-Cyano-7-deazainosine has low toxicity and thus is a perfect tool to explore cAMP-independent PKA signaling in these important pathogens. This project describes PKA-induced phosphoproteome changes of the bloodstream stage of T. brucei.
2019-02-25 | PXD012245 | Pride
Project description:BackgroundAppropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death.ResultsWe present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1.ConclusionsWe propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast.
| S-EPMC3001716 | biostudies-literature
Project description:Intrinsic abnormalities in transplanted eutopic endometrium are believed to contribute to the pathogenesis of pelvic endometriosis. Herein, we investigated transcriptomic differences in human endometrial stromal fibroblasts (hESF) from women with (hESFendo) versus without (hESFnon-endo) endometriosis, in response to activation of the PKA pathway with 8-Br-cAMP. hESFnon-endo (n=4) and hESFendo (mild endometriosis, n=4) were isolated from eutopic endometrium and treated +/- 0.5mM 8-Br-cAMP for 96 hours. Purified total RNA was subjected to microarray analysis using the whole genome Gene 1.0 ST Affymetrix platform. 733 genes were regulated in cAMP-treated hESFnon-endo versus 172 genes in hESFendo, suggesting a blunted response to cAMP/PKA pathway activation in women with disease. Real-time PCR and ELISA validated the decreased expression of decidualization markers in hESFendo compared to hESFnon-endo. In the absence of disease, 8-Br-cAMP down-regulated progression through the cell-cycle due to a decrease in Cyclin D1, cyclin-dependent kinase 6 and cell division cycle 2, and an increase in cyclin-dependent kinase inhibitor 1A. However, cell cycle components in hESFendo were not responsive to 8-Br-cAMP, resulting in persistence of a proliferative phenotype. hESFendo treated with 8-Br-cAMP exhibited altered expression of immune response, extracellular matrix, cytoskeleton, and apoptosis genes. Changes in phosphodiesterase expression and activity were not different among experimental groups. Thus, eutopic hESF with increased proliferative potential may seed the pelvic cavity via retrograde menstruation and promote establishment, survival, and proliferation of endometriosis lesions, independent of hydrolysis of cAMP and likely due to an inherent abnormality in the PKA pathway in the presence of disease.
2009-12-19 | GSE17504 | GEO
Project description:Frozen dough baking is useful method in the modern bread-making industry. However, the fermentation activity of bakerâs yeast dramatically decreased after thawing due to freeze injuries, because bakerâs yeast cells contained in dough experience freeze injuries during freeze-thaw processes. Here, we performed genome-wide expression analysis to determine genetic response in bakerâs yeasts under freeze-thaw condition using a DNA microarray analysis. Functional and clustering analyses in gene expression reveal that genes could be characterized by the term of freeze-thaw stress. Under short-term freeze stress (freeze treatment for 3 day), genes involved in ribosomal protein were up-regulated. Under long-term freeze stress (freeze treatment for longer than 7 day), genes involved in energy synthesis were up-regulated. In each phase, genes involved in protein damage, several stresses and trehalose and glycogen metabolism were also up-regulated. Through these freeze stress, yeast cells may improve reduced efficiency of translation and enhanced cell protection mechanism to survive under freeze stress condition. These regulations of these genes would be controlled by the cAMP-protein kinase A pathway. Experiment Overall Design: All experiments were done in duplicate from two independent samples.
2009-08-09 | E-GEOD-8673 | biostudies-arrayexpress
Project description:Protein kinase A (PKA), the main effector of second messenger cAMP, is highly conserved among eukaryotes and a paradigm for the mechanisms of regulation of protein kinases by ligands. The unique PKA holoenzymes in the phylogenetically distant protozoan parasite Trypanosoma are unresponsive to cAMP in vitro and in vivo. By small molecule screening and optimization, we designed direct, membrane-permeable activators binding with a kD of 9 nM to the CNB pockets of the T. brucei regulatory PKA subunit. 7-Cyano-7-deazainosine has low toxicity and thus is a perfect tool to explore cAMP-independent PKA signaling in these important pathogens. This project describes the PKA-inducible proteome of the bloodstream stage of T. brucei.
2019-02-25 | PXD009073 | Pride
Project description:Human mesenchymal stromal cells (hMSCs) are able to differentiate into a wide variety of cell types, which makes them an interesting source for tissue engineering applications. On the other hand, these cells also secrete a broad panel of growth factors and cytokines that can exert trophic effects on surrounding tissues. In bone tissue engineering applications, the general assumption is that direct differentiation of hMSCs into osteoblasts accounts for newly observed bone formation in vivo. However, the secretion of bone-specific growth factors, but also pro-angiogenic factors, could also contribute to this process. We recently demonstrated that secretion of bone specific growth factors can be enhanced by treatment of hMSCs with the small molecule db-cAMP (cAMP) and here we investigate the biological activity of these secreted factors. We demonstrate that conditioned medium contains a variety of secreted growth factors, with differences between medium from basic-treated and cAMP-treated hMSCs. We show that conditioned medium from cAMP-treated hMSCs increases proliferation of various cell types and also induces osteogenic differentiation, whereas it has differential effects on migration. Microarray analysis on hMSCs exposed to conditioned medium confirmed upregulation of pathways involved in proliferation as well as osteogenic differentiation. Our data suggests that trophic factors secreted by hMSCs can be tuned for specific applications and that a good balance between differentiation on the one hand and secretion of bone trophic factors on the other, could potentially enhance bone formation for bone tissue engineering applications. For more information check: https://cbit.maastrichtuniversity.nl/
2018-10-06 | E-MTAB-7224 | biostudies-arrayexpress
Project description:Cyclic AMP activates two downstream factors, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC) and both downstream signalings induce syncytialization, cell fusion and the production of hCG and progesterone. We used microarray to identify novel transcription factors related to syncytialization in two cAMP signaling-stimulated BeWo cells.
2017-09-30 | GSE100095 | GEO
Project description:EPAC1, a cAMP-activated GEF for Rap GTPases, is a major transducer of cAMP signaling in normal cells and a therapeutic target in cardiac diseases. The recent discovery that cAMP is compartmentalized in membrane-proximal nanodomains challenged the current model of EPAC1 activation in the cytosol. Here, we discover that anionic membranes are a major component of EPAC1 activation. We find that anionic membranes activate EPAC1 in the absence of cAMP, that they increase its affinity for cAMP by 2 orders of magnitude, and that they synergize with cAMP to yield maximal GEF activity. Thus, EPAC1 has four states that differ in their affinity for cAMP and GEF efficiency. In cells, where cytosolic cAMP is low, this implies that EPAC1 must be primed by membranes to bind cAMP. Examination of the inhibitory mechanism of the cardiomyocyte-active chemical CE3F4 in this new framework further reveals that it targets only only membrane- and cAMP-activated EPAC1. Together, our findings reformulate previous concepts of cAMP signaling to include a hitherto overlooked role of membranes through EPAC proteins, with important implications for drug discovery.
2023-04-07 | PXD040227 | Pride
Project description:Signal transduction plays a crucial role in defending against external environmental challenges, which can modulate the cellular response to external stimuli. cAMP/PKA signaling pathway is one of the most important signaling circuits and is evolutionarily conserved in eukaryotes. A. oligospora is a typical nematode-trapping fungi that can specialize adhesive network traps to kill nematodes after sensing the signals. To elucidate the biological roles of cAMP-PKA signaling pathway, we characterized an adenylate cyclase orthologous protein, AoAcy, a cAMP-dependent protein kinase regulator, AoPKaR, and two cAMP-dependent protein kinase catalytic subunits, AoPKaCs in A. oligospora. Furthermore, phenotypic analysis of the gene disruption strains showed that the deletion of AoAcy resulted in a significant decrease in the content of cAMP and arthrobotrisins, and the results indicated that AoAcy, AoPKaR and AoPKaC1 were involved in the hyphae growth, trap morphogenesis, sporulation, stress resistance and autophagy. In addition, AoAcy and AoPKaC1 were also participated in the regulation of mitochondria, thereby affecting energy metabolism. While AoPKaC2 only affected sporulation, the number of nuclei and autophagy. Collectively, these findings highlight the essential role of cAMP/PKA signaling pathway in A. oligospora and provide insights into the regulation mechanisms of signaling pathways in trap formation and sporulation.
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