Transcriptomic, (phospho)proteomic, and metabolomic analysis of tumor-comprising cells treated by photodynamic therapy
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD004320PRJNA331051PRJNA331048PRJNA331050
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE84758 | GEO | 2016/11/25
SECONDARY ACCESSION(S): PRJNA331048
REPOSITORIES: GEO
Similar Datasets
Project description:Photodynamic therapy (PDT) is a tumor treatment strategy that relies on the production of reactive oxygen species (ROS) in the tumor following local illumination. Although PDT has shown promising results in the treatment of non-resectable perihilar cholangiocarcinoma, it is still employed palliatively. In this study, tumor-comprising cells (i.e., cancer cells, endothelial cells, macrophages) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). Post-PDT survival pathways were studied following sublethal (50% lethal concentration (LC50)) and supralethal (LC90) PDT using a multi-omics approach. ZPCLs did not exhibit toxicity in any of the cells as assessed by toxicogenomics. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly hypoxia-inducible factor 1 (HIF-1)-, nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB)-, activator protein 1 (AP-1)-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. (Phospho)proteomic and metabolomic analysis showed that PDT-subjected SK-ChA-1 cells downregulated proteins associated with epidermal growth factor receptor (EGFR) signaling, particularly at LC50. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor parenchymal and non-parenchymal cells that, in tumor cells, transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, sublethally afflicted tumor cells are a major therapeutic culprit. Our multi-omics analysis unveiled multiple druggable targets for pharmacological intervention.
2016-11-25 | GSE84757 | GEO
Project description:Photodynamic therapy (PDT) is a tumor treatment strategy that relies on the production of reactive oxygen species (ROS) in the tumor following local illumination. Although PDT has shown promising results in the treatment of non-resectable perihilar cholangiocarcinoma, it is still employed palliatively. In this study, tumor-comprising cells (i.e., cancer cells, endothelial cells, macrophages) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). Post-PDT survival pathways were studied following sublethal (50% lethal concentration (LC50)) and supralethal (LC90) PDT using a multi-omics approach. ZPCLs did not exhibit toxicity in any of the cells as assessed by toxicogenomics. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly hypoxia-inducible factor 1 (HIF-1)-, nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB)-, activator protein 1 (AP-1)-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. (Phospho)proteomic and metabolomic analysis showed that PDT-subjected SK-ChA-1 cells downregulated proteins associated with epidermal growth factor receptor (EGFR) signaling, particularly at LC50. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor parenchymal and non-parenchymal cells that, in tumor cells, transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, sublethally afflicted tumor cells are a major therapeutic culprit. Our multi-omics analysis unveiled multiple druggable targets for pharmacological intervention.
2016-11-25 | GSE84756 | GEO
Project description:Transcriptomic, (phospho)proteomic, and metabolomic analysis of tumor-comprising cells treated by photodynamic therapy
| PRJNA331048 | ENA
Project description:Background: Recent evidence has shown that the long non-coding RNA (lncRNA) rPvt1 is elevated in septic myocardial tissues and that its knockdown attenuates sepsis-induced myocardial injury. However, the mechanism underlying the role of rPvt1 in septic myocardial dysfunction has not been elucidated. Methods: In this study, we performed transcriptomic, proteomic, and metabolomic assays and conducted an integrated multi-omics analysis to explore the association between rPvt1 and lipopolysaccharide (Lipopolysaccharide)-induced H9C2 cardiomyocyte injury. LncRNA rPvt1 silencing was achieved using a lentiviral transduction system. Results: Compared to those with the negative control, rPvt1 knockdown led to large changes in the transcriptome, proteome, and metabolome. Specifically, 2,385 differentially expressed genes (DEGs), 272 differentially abundant proteins and 75 differentially expressed metabolites (DEMs) were identified through each omics analysis, respectively. Gene Ontology functional annotation, Kyoto Encyclopedia of Genes and Genomes, Nr, eukaryotic orthologous groups, and Clusters of Orthologous Groups of Proteins pathway analyses were performed on these differentially expressed/abundant factors. The results suggested that mitochondrial energy metabolism might be closely related to the mechanism through which Pvt1 functions. Conclusion: These genes, proteins, metabolites, and their related dysregulated pathways could thus be promising targets for studies investigating the rPvt1-regluatory mechanisms involved in septic myocardial dysfunction, which is important for formulating novel strategies for the prevention, diagnosis and treatment of septic myocardial injury.
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Project description:We report the application of 5-ALA ( 5-Aminolevulinic acid)-mediated photodynamic therapy on mouse brain tissue, and further explored the impact of PDT on nervous system.
2021-04-30 | GSE173615 | GEO
Project description:Cardiac dyssynchrony arises from conduction abnormalities during heart failure and worsens morbidity and mortality. Cardiac resynchronization therapy (CRT) re-coordinates contraction using bi-ventricular pacing, but the cellular and molecular mechanisms involved remain largely unknown. The aim is to determine how dyssynchronous heart failure (HFdys ) alters the phospho-proteome and how CRT interacts with this unique phospho-proteome by analyzing Ser/Thr and Tyr phosphorylation. Phospho-enriched myocardium from dog models of Control, HFdys , and CRT is analyzed via MS. There were 209 regulated phospho-sites among 1761 identified sites. Compared to Con and CRT, HFdys is hyper-phosphorylated and tyrosine phosphorylation is more likely to be involved in signaling that increased with HFdys and was exacerbated by CRT. For each regulated site, the most-likely targeting-kinase is predicted, and CK2 is highly specific for sites that are "fixed" by CRT, suggesting activation of CK2 signaling occurs in HFdys that is reversed by CRT, which is supported by western blot analysis. These data elucidate signaling networks and kinases that may be involved and deserve further study. Importantly, a possible role for CK2 modulation in CRT has been identified. This may be harnessed in the future therapeutically to compliment CRT, improving its clinical effects.
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Project description:We report the application of Porfimer sodium-mediated photodynamic therapy on mouse brain endothelial cells, and further identified the impact of PDT on the normal vessel cells.
2021-04-17 | GSE172198 | GEO
Project description:This study looked for signals produced in UV-B irradiated leaves, and possibly induced in shielded leaves, that modulate physiological responses in maize. Transcriptome and proteomics profiling tracked changes in exposed and shielded organs. Metabolic profiling was examined for signaling molecules. Exposure of just the top leaf substantially alters the transcriptome of both irradiated and shielded organs, with greater changes as an additional 1-2 leaves are irradiated. Transcriptome, proteome and metabolome changes are UV-B regulated in shielded organs. Early steps in signal transduction and possible signal molecules are identified utilizing a time course experiment. Keywords: UVB, maize, leaves, ears Compared irradiated leaves in a time course, irradiated leaves versus shielded leaves, and shielded ears on plants with irradiated leaves. Also compared different number of leaves being irradiated. Spike-in controls were included.
2011-02-01 | E-GEOD-25038 | biostudies-arrayexpress
Project description:BACKGROUND: Clostridium thermocellum is a candidate consolidated bioprocessing biocatalyst, which is a microorganism that expresses enzymes for both cellulose hydrolysis and its fermentation to produce fuels such as lignocellulosic ethanol. However, C. thermocellum is relatively sensitive to ethanol compared to ethanologenic microorganisms such as yeast and Zymomonas mobilis that are used in industrial fermentations but do not possess native enzymes for industrial cellulose hydrolysis. RESULTS: In this study, C. thermocellum was grown to mid-exponential phase and then treated with ethanol to a final concentration of 3.9 g/L to investigate its physiological and regulatory responses to ethanol stress. Samples were taken pre-shock and 2, 12, 30, 60, 120, and 240 min post-shock, and from untreated control fermentations for systems biology analyses. Cell growth was arrested by ethanol supplementation with intracellular accumulation of carbon sources such as cellobiose, and sugar phosphates, including fructose-6-phosphate and glucose-6-phosphate. The largest response of C. thermocellum to ethanol shock treatment was in genes and proteins related to nitrogen uptake and metabolism, which is likely important for redirecting the cells physiology to overcome inhibition and allow growth to resume. CONCLUSION: This study suggests possible avenues for metabolic engineering and provides comprehensive, integrated systems biology datasets that will be useful for future metabolic modeling and strain development endeavors.
| S-EPMC3478167 | biostudies-literature
Project description:BackgroundUnder normal solar fluence, UV-B damages macromolecules, but it also elicits physiological acclimation and developmental changes in plants. Excess UV-B decreases crop yield. Using a treatment twice solar fluence, we focus on discovering signals produced in UV-B-irradiated maize leaves that translate to systemic changes in shielded leaves and immature ears.ResultsUsing transcriptome and proteomic profiling, we tracked the kinetics of transcript and protein alterations in exposed and shielded organs over 6 h. In parallel, metabolic profiling identified candidate signaling molecules based on rapid increase in irradiated leaves and increased levels in shielded organs; pathways associated with the synthesis, sequestration, or degradation of some of these potential signal molecules were UV-B-responsive. Exposure of just the top leaf substantially alters the transcriptomes of both irradiated and shielded organs, with greater changes as additional leaves are irradiated. Some phenylpropanoid pathway genes are expressed only in irradiated leaves, reflected in accumulation of pathway sunscreen molecules. Most protein changes detected occur quickly: approximately 92% of the proteins in leaves and 73% in immature ears changed after 4 h UV-B were altered by a 1 h UV-B treatment.ConclusionsThere were significant transcriptome, proteomic, and metabolomic changes under all conditions studied in both shielded and irradiated organs. A dramatic decrease in transcript diversity in irradiated and shielded leaves occurs between 0 h and 1 h, demonstrating the susceptibility of plants to short term UV-B spikes as during ozone depletion. Immature maize ears are highly responsive to canopy leaf exposure to UV-B.
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