Effects on renal senescence, copper flux and respiration during stem cell-based therapy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1274853 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR33945939_1.fastq.gz | Fastqsanger.gz | |||
| SRR33945939_2.fastq.gz | Fastqsanger.gz | |||
| SRR33945941_1.fastq.gz | Fastqsanger.gz | |||
| SRR33945941_2.fastq.gz | Fastqsanger.gz |
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Project description:Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can reverse senescence after acute kidney injury (AKI) via maintaining mitochondrial homeostasis. Copper accumulation could promote senescence, but its response to MSCs remains unclear. C57 mice with renal unilateral ischemia reperfusion injury (uIRI) were renal capsular transplanted with hUC-MSCs for two weeks then performed mRNA sequencing. Gene correlation analysis revealed that senescence regulation is associated with copper homeostasis and respiratory chain complex IV.
2025-06-18 | GSE299500 | GEO
Project description:Copper (Cu) is an essential trace element required for mitochondrial respiration. We show that Cu drives coordinated metabolic remodeling of bioenergy, biosynthesis and redox homeostasis and progression of clear cell renal cell carcinoma (ccRCC). Cu stimulates tumor growth. Late-stage ccRCCs accumulate Cu and allocate it to cytochrome c oxidase stimulating bioenergy production. Cu induces TCA cycle-dependent oxidation of glucose and its utilization for biosynthesis of a glutathione pool that protects against H2O2 generated during mitochondrial respiration, therefore coordinating bioenergy production with redox protection.
2024-10-18 | GSE250028 | GEO
Project description:Copper (Cu) is an essential trace element required for mitochondrial respiration. We show that Cu drives coordinated metabolic remodeling of bioenergy, biosynthesis and redox homeostasis and promotes tumor growth and progression of clear cell renal cell carcinoma (ccRCC). Late-stage ccRCCs accumulate Cu and allocate it to cytochrome c oxidase stimulating bioenergy production. Cu induces TCA cycle-dependent oxidation of glucose and its utilization for biosynthesis of a glutathione pool that protects against H2O2 generated during mitochondrial respiration, therefore coordinating bioenergy production with redox protection. Single cell transcriptomics determined induction of mitochondrial electron transport chain, expression of NRF2 targets and glutathione biosynthesis, and decrease in HIF activity, the hallmark of ccRCC, during disease progression. Spatial transcriptomics identified that cancer cells with proliferative phenotype are embedded in clusters of cells with oxidative metabolism supporting effects of metabolic states on ccRCC progression. Our work establishes novel vulnerabilities with potential for therapeutic interventions in ccRCC.
2024-10-18 | GSE250163 | GEO
Project description:Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes including respiration, photosynthesis and oxidative stress protection. In many eukaryotic organisms, including yeast and mammals, copper and iron homeostases are highly interconnected; however such interdependence is not well established in higher plants. Here we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis thaliana. COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We have characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 expression could play a dual role under Fe deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation maybe aimed to minimize further iron consume. On the other hand, global expression analyses of copt2-1 mutants versus wild type Arabidopsis plants indicate that low phosphate responses are increased in copt2-1 plants. In this sense, COPT2 function under Fe deficiency counteracts low phosphate responses. These results open up new biotechnological approaches to fight iron deficiency in crops.
2013-06-05 | GSE42642 | GEO
Project description:A 3 x 2 factorial design was used to elucidate the genome-wide transcriptional response to the deletion of yeast ortholog of Wilson and Menkes disease causing gene; CCC2, at changing copper levels. Homozygous deletion mutant of CCC2, which encodes Cu+2 transporting P-type ATPase required to export copper from the cytosol into the extracytosolic compartment, and the reference strain were cultivated in fully controlled fermenters in duplicates in glucose-rich defined medium containing three different levels of copper. The three different copper concentrations were selected such that; copper deficient condition, which was prepared by excluding the CuSO4.7H2O from the defined medium, low copper or adequate copper concentration, which is the standard amount of copper in defined medium (0.04 ?M) and high copper concentration (0.5 mM), which was able to restore respiration deficiency in ccc2?/ccc2? strain.
2013-09-02 | E-MEXP-3927 | biostudies-arrayexpress
Project description:Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes including respiration, photosynthesis and oxidative stress protection. In many eukaryotic organisms, including yeast and mammals, copper and iron homeostases are highly interconnected; however such interdependence is not well established in higher plants. Here we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis thaliana. COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We have characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 expression could play a dual role under Fe deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation maybe aimed to minimize further iron consume. On the other hand, global expression analyses of copt2-1 mutants versus wild type Arabidopsis plants indicate that low phosphate responses are increased in copt2-1 plants. In this sense, COPT2 function under Fe deficiency counteracts low phosphate responses. These results open up new biotechnological approaches to fight iron deficiency in crops. Four biological replicates of Arabidopsis seedlings were generated for 2 genotypes, Col-0 and copt2-1 mutant; and 3 growth condictions; first one an iron(Fe) and copper(Cu) sufficient medium (+Fe + Cu), second one an Fe deficient and Cu sufficient medium (-Fe+Cu) and third one an Fe and Cu deficient medium (-Fe-Cu). For each growth one comparasion was made, copt2-1 mutant versus Col-0; in each comparasion four biological replicates were made, two replicas were labeled with Cy5 for the mutant sample and Cy3 for the Col-0 sample, while the other two replicas were reversed-labeled.
2013-06-05 | E-GEOD-42642 | biostudies-arrayexpress
Project description:Kidney is a vital organ responsible for homeostasis in the body. To retard kidney aging is of great importance for maintaining body health. Whereas the therapeutic strategies targeting against kidney aging are not elucidated. Recent studies show mitochondrial dysfunction is critical for renal tubular cell senescence and kidney aging, however, the underlying mechanisms of mitochondrial dysfunction in kidney aging have not been demonstrated. Herein, we found calcium overload, and the mitochondrial calcium uniporter (MCU) was induced in renal tubular cells and aged kidney. To activate MCU not only triggered mitochondrial calcium overload, but also induced reactive oxygen species (ROS) production and cellular senescence and age-related kidney fibrosis. Inversely, to block MCU or chelate calcium diminished ROS generation, restored mitochondrial homeostasis, and retarded cell senescence and protected against kidney aging. These results demonstrate MCU plays a key role in promote renal tubular cell senescence, which provides a new insight on the therapeutic strategy for fighting against kidney aging.
2024-10-02 | GSE262514 | GEO
Project description:The copper reductase activity of histone H3 suggests the presence of yet-to-be-discovered characteristics within the protein. Here, we investigated the function of leucine 126 (H3L126), which serves as the axial ligand for copper binding. Typically found as a methionine or leucine in copper binding proteins, the axial ligand influences the reduction potential of the bound ion, thereby modulating the capability of a protein to conduct electrons. Mutation of H3L126 to methionine (H3L126M) increased the enzymatic activity of yeast nucleosomes and intracellular Cu1+ levels, leading to improved copper-dependent activities including mitochondrial respiration and growth in oxidative media with low copper. H3L126 to histidine (H3L126H) mutation decreased nucleosome’s enzymatic activity and resulted in opposite phenotypes in vivo. Our findings demonstrate the role of H3L126 in fine-tuning the copper reductase activity of nucleosomes and underscore the utility of nucleosome enzymatic activity as a novel paradigm to uncover previously unnoticed features of histones.
2023-12-31 | GSE243833 | GEO
Project description:Background: Despite endothelial dysfunction being considered as the initial step of the development of hypertension and associated cardio-renal syndromes, effective therapeutic strategies to prevent endothelial injuries are still lacking. GPR183 is a recently identified GPCR for oxysterols and hydroxylated metabolites of cholesterol. Here, we explored a previously unappreciated role of GPR183 in hypertension and age-related cardio-renal injuries. Methods and results: Mice were treated with DOCA/Salt or AngII to induce hypertension. we found that endothelial GPR183 was significantly induced in aged or hypertensive mice, which was further confirmed in renal biopsies from elderly people or subjects with hypertensive nephropathy. In addition, we found that endothelial-specific GPR183 deletion markedly ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Mechanistically, we found that GPR183 disrupted circadian signaling by inhibiting PER1 expression, thereby facilitating endothelial senescence and dysfunction through the cAMP/PKA/CREB signaling pathway. Importantly, pharmacological inhibition of the oxysterol-GPR183 axis by NIBR189 or Clotrimazole ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Conclusions: GPR183 is an attractive therapeutic target for hypertension and age-related diseases. Targeting GPR183 could provide novel strategies for managing hypertension and its associated cardio-renal injuries.
2024-06-23 | GSE270175 | GEO
Project description:Copper is an essential component of cytochrome C oxidase (i.e. complex IV of the electron transport chain), and is thus critical for the survival of aerobic organisms. If copper is not properly regulated in the body however, it can be extremely cytotoxic and genetic mutations that compromise copper homeostasis result in severe clinical phenotypes. Understanding how cells maintain optimal copper levels is therefore highly relevant to human health. We found that addition of copper to culture medium leads to increased respiratory growth of yeast, a phenotype which we then systematically and quantitatively measured in 5050 homozygous diploid deletion strains using microarrays. In the yeast homozygous gene deletion collection, both copies of every non-essential gene are deleted in a diploid strain. Each strain contains unique 20-bp M-bM-^@M-^\barcodeM-bM-^@M-^] sequences flanked by common priming sites, allowing the relative abundance of individual strains to be quantitatively monitored within a pool of competitively-grown strains. To identify genes that are important for Cu-dependent respiratory growth, we measured the fitness of 5050 homozygous deletion strains in parallel in rich media (i.e. Yeast Extract, Peptone) using either dextrose, ethanol, glycerol, or lactate as a carbon source, in the presence or absence of 500 M-BM-5M CuSO4 for 9 generations. Each condition was tested in triplicate. Please note that there is a large percentage of null-values (i.e. Not Available) in the respiration deficient-pool samples because the respiration deficient pool consists of only a small subset of the complete pool (represented by 331 barcodes instead of 9937). For our analysis we discarded the remaining barcodes by assigning the null-value to them.
2013-05-23 | E-GEOD-47175 | biostudies-arrayexpress