GNPS - Piperlongumine comigration analyses of de novo extracts of Gymnoteca chinensis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Exploris 120
ORGANISM(S): Gymnoteca Chinensis
SUBMITTER: 
Jean-Luc Wolfender
PROVIDER: MSV000097611 | GNPS | Sun Apr 13 04:19:00 BST 2025
REPOSITORIES: GNPS
Similar Datasets
Project description:The de novo extracts of G. chinensis were subjected to UHPLC-CAD-HRMS, which showed that both the retention time and MS/MS matched between the extract and the piperlongumine standard
2025-04-13 | MSV000097611 | MassIVE
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis
2008-12-01 | GSE9820 | GEO
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis In total 153 arrays were analyzed with 6 technical replicates (147 biological samples). CD34+ stem cells, CD4+ T-cells, resting CD14+ monocytes, stimulated monocytes and macrophages were analyzed, all from patient with severe coronary atherosclerosis or controls that had no coronary atherosclerosis as determined angiographically, and which were carefully matched for age and gender.
2008-12-01 | E-GEOD-9820 | biostudies-arrayexpress
Project description:Pleural mesothelioma (PM) is one of the deadliest cancers, with limited therapeutic options due to its therapeutically intractable genome, which is characterized by the functional inactivation of tumor suppressor genes (TSGs) and high tumor heterogeneity, including diverse metabolic adaptations. However, the molecular mechanisms underlying these metabolic alterations remain poorly understood, particularly how TSG inactivation rewires tumor metabolism to drive tumorigenesis and create metabolic dependencies. Through integrated multi-omics analysis, we identify for the first time that NF2 loss of function defines a distinct PM subtype characterized by enhanced de novo pyrimidine synthesis, which NF2-deficient PM cells are critically dependent on for sustained proliferation in vitro and in vivo. Mechanistically, NF2 loss activates YAP, a downstream proto-oncogenic transcriptional coactivator in the Hippo signalling pathway, which in turn upregulates CAD and DHODH, key enzymes in the de novo pyrimidine biosynthesis pathway. Our findings provide novel insights into metabolic reprogramming in PM, revealing de novo pyrimidine synthesis as a synthetic lethal vulnerability in NF2-deficient tumors. This work highlights a potential therapeutic strategy for targeting NF2-deficient mesothelioma through metabolic intervention.
2025-07-08 | PXD063342 | Pride
Project description:Metabolic heterogeneity resulting from the intrinsic heterogeneity of human tumors has been shown to cause a myriad of adverse outcomes of tumor therapy, including resistance to chemotherapy, but the mechanisms inside remain largely unknown. Here, we found that the de novo pyrimidine synthesis pathway, which we previously identified as crucial for the proliferation of gastric and colon cancer cells, determines the chemosensitivity of these cancer types. In the chemosensitive cells, chemotherapeutic drugs such as 5-FU promoted the degradation of CAD, an enzyme that is rate-limiting for pyrimidine synthesis, leading to the apoptosis of these cells. We also found that CAD needed to be cleaved, by activated caspase-3 on its Asp1371 residue, before its degradation. Upregulation of CAD, either by overexpression or by a mutation on the Asp1371 to block the caspase-3 cleavage, conferred tumor chemoresistance in both mouse xenograft models and the Cldn18-ATK mouse gastric tumor models. Importantly, mutations related to Asp1371 of CAD were found in gastric tumor samples of patients who underwent unsuccessful neoadjuvant chemotherapy. By searching for a compound that is capable of degradating the CAD-Asp1371 mutant, we discovered that a compound called RMY-186 can be used to treat chemoresistant tumors related to CAD mutations, resulting in a significant improvement in the effectiveness of chemotherapy. We have, therefore, revealed the vulnerability of de novo pyrimidine synthesis during chemotherapy, which can be targeted to overcome chemotherapeutic resistance and augment the antitumor efficacy of genotoxic chemotherapy agents.
2025-01-01 | PXD059365 |
Project description:De novo pyrimidine biosynthesis is achieved by cytosolic enzymes, CAD and UMPS, and mitochondrial DHODH. However, how these enzymes are orchestrated remains enigmatical. Here, we show that cytosolic aspartate-producing GOT1 clusters with CAD and UMPS. This cytosolic cluster then connects with DHODH, which is mediated by the mitochondrial outer membrane channel protein VDAC3. Therefore, these proteins form a multi-enzyme complex, named “pyrimidinosome”, involving AMPK as a regulator. Activated AMPK dissociates from the complex, enhancing pyrimidinosome assembly to up-regulate intermediate orotate synthesis, which promotes DHODH-mediated ferroptosis defense. In contrast, pyrimidinosome-mediated UMP biosynthesis is significantly increased in cells lacking AMPK, so that cancer cells with lower expression of AMPK are more reliant on de novo pyrimidine biosynthesis and more vulnerable to its inhibition in vitro and in vivo. Our findings reveal the role of pyrimidinosome in regulating pyrimidine flux and ferroptosis, and suggest a pharmaceutical strategy of targeting pyrimidinosome in cancer treatment.
2023-03-22 | PXD041017 |
Project description:Protein deamidation is emerging as a post-translational modification that regulates protein function. The general role of protein deamidation is emerging asn fundamental to biological processes, yet remains is poorly understood. Here, we report that the rate-limiting enzyme of pyrimidine synthesis, a trifunctional enzyme containing activity of carbamoyl phosphate synthetase, aspartyl transcarbamoylase and dihydroorotase (CAD), deamidates the RelA subunit to inactivate NF-κB and promote glycolysis. Functional screening and identified CAD as a negative regulator of NF-κB activation, and biochemical analysis demonstrated that CAD deamidatesd RelA in vitro and in cellsto negate NF-κB activation. D eamidated RelA, though failed to activate the expression of NF-κB-dependent genes, thoughbut it up-regulated that of key glycolytic enzymes to promote glycolysis and cell proliferation. In proliferating cells, CAD is activated and catalyzes de novo pyrimidine synthesis to meet the metabolic need during S phase. CAD-mediated RelA deamidation and NF-κB inactivation and glycolytic gene expression paralleled in a cell cycle-dependent mannerdriven by CAD-mediated RelA deamidation are necessary for cell proliferation. In addition, CAD promoted glycolysis via deamidated RelA that up-regulated the expression of key glycolytic enzymes. Stratification of cancer cell lines by CAD-mediated RelA deamidation predicted their sensitivity to inhibitors of glycolytic enzymes, while a subset of mutations predisposed RelA to deamidation and promoted glycolysis to enable cell proliferation. This work describes a process of metabolic reprogramming enabled by CAD-mediated RelA deamidation that underpins cell proliferation and tumorigenesis.
2019-11-01 | GSE132868 | GEO
Project description:Protein deamidation is emerging as a post-translational modification that regulates protein function. The general role of protein deamidation is emerging asn fundamental to biological processes, yet remains is poorly understood. Here, we report that the rate-limiting enzyme of pyrimidine synthesis, a trifunctional enzyme containing activity of carbamoyl phosphate synthetase, aspartyl transcarbamoylase and dihydroorotase (CAD), deamidates the RelA subunit to inactivate NF-κB and promote glycolysis. Functional screening and identified CAD as a negative regulator of NF-κB activation, and biochemical analysis demonstrated that CAD deamidatesd RelA in vitro and in cellsto negate NF-κB activation. D eamidated RelA, though failed to activate the expression of NF-κB-dependent genes, thoughbut it up-regulated that of key glycolytic enzymes to promote glycolysis and cell proliferation. In proliferating cells, CAD is activated and catalyzes de novo pyrimidine synthesis to meet the metabolic need during S phase. CAD-mediated RelA deamidation and NF-κB inactivation and glycolytic gene expression paralleled in a cell cycle-dependent mannerdriven by CAD-mediated RelA deamidation are necessary for cell proliferation. In addition, CAD promoted glycolysis via deamidated RelA that up-regulated the expression of key glycolytic enzymes. Stratification of cancer cell lines by CAD-mediated RelA deamidation predicted their sensitivity to inhibitors of glycolytic enzymes, while a subset of mutations predisposed RelA to deamidation and promoted glycolysis to enable cell proliferation. This work describes a process of metabolic reprogramming enabled by CAD-mediated RelA deamidation that underpins cell proliferation and tumorigenesis.
2019-11-01 | GSE132871 | GEO
Project description:Aerobic glycolysis, which is also termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. To date, no studies have explored interrelationships between glycolysis and other metabolic pathways. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three steps of de novo pyrimidine synthesis. PFKFB3 inactivation reduced de novo pyrimidine synthesis, RNA and DNA production, and the growth of cancer and proliferative cells. Thus, the glycolytic activator PFKFB3 bridges glycolysis with pyrimidine synthesis, unites both glucose metabolism and nucleic acid metabolism, and contributes to cell proliferation under both physiological and pathological conditions.
2025-06-16 | PXD048755 | Pride
Project description:we analysed the whole epigenomic profile of different blood subtypes, neutrophiles, monocytes, lymphocytes B and T, from 5 de novo and drug-naïve PD patients and 5 age and gender matched healthy control.
2023-11-01 | GSE122244 | GEO