Proteomic validation of cell death mechanisms of HDQ-mediated copper transporting
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Xiang Li
PROVIDER: PXD075646 | iProX | Fri Mar 13 00:00:00 GMT 2026
REPOSITORIES: iProX
Similar Datasets
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: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:Wilson disease (WD) is a severe metabolic disorder caused by genetic inactivation of copper-transporting ATPase ATP7B. In WD, copper accumulates in several tissues, particularly in the liver, inducing marked time-dependent pathological changes. To identify initial events in the copper-dependent development of liver pathology we utilized the Atp7b-/- mice, an animal model for WD. Analysis of mRNA from livers of control and Atp7b-/- 6 weeks-old mice using oligonucleotide arrays revealed specific changes of the transcriptome at this stage of copper accumulation. Few messages (29 up-regulated and 46 down-regulated) change their abundance more than 2-fold pointing to the specific effect of copper on gene expression/mRNA stability. The gene ontology analysis revealed copper effects on distinct metabolic pathways. Keywords: comparative genomic hybridization
2006-12-19 | GSE5348 | GEO
Project description:In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1. Ace1 mediates Cu-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mac1 activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YJL217w and YFR055w. Two of the last three newly identified Mac1 target genes have no known function, the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mac1, designated Mac1up1, are not direct targets of Mac1. Induction or repression of these genes is likely a secondary effect of cells due to constitutive Mac1 activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5, and two genes, FET3 and FTR1, in the iron uptake system. Cu-induced FET3 and FTR1 expression arises from an indirect Cu effect on cellular Fe pools. This study is described in more detail in Gross C et al.(2000) J Biol Chem 275:32310-6 Keywords: other
2002-02-12 | GSE26 | GEO
Project description:The cyanobacterium Microcystis aeruginosa PCC 7806 was used for a systematic survey of the relationship between copper and microcystins synthesis. Here we have used microarrays to interrogate the global responses to copper additions at 0.5 micromolar (µM) and 3 µM of copper. From the gene level, microarray studies (3 µM copper supplementation) showed effects on iron, sulfur, glutaredoxin and dehydratase homeostasis gene expression. However, in 0.5 µM groups, those genes that significantly enriched in 3 µM groups regulatory were not all found. In the microarray data for copper stress (3 µM) revealed a broad effect on the expression of iron-sulphur cluster associated pathways, such as cysteine biosynthesis. All of these data indicate that Fe / S cluster biogenesis and/or repair were affected by copper in M. aeruginosa.
2018-12-21 | GSE108380 | GEO
Project description:As an essential micronutrient element in organisms, copper controls a host of fundamental cellular functions. Recently, copper-dependent cell growth and proliferation have been defined as "cuproplasia". Conversely, “cuproptosis” represents copper-dependent cell death, a nonapoptotic manner. So far, a series of copper ionophores have been developed to kill cancer cells. However, the biological response mechanism of copper uptake still lacks systematic analysis. Based on quantitative proteomics, we revealed the crosstalk between copper stress and cuproptosis in cancer cells. Copper stress not only couples with cuproptosis, but also leads to reactive oxygen species (ROS) stress, oxidative damage and cell cycle arrest. In cancer cells, a feedback cytoprotection mechanism involving cuproptosis mediators was discovered. During copper treatment, the activation of glutamine transporters and the loss of Fe-S cluster proteins are the facilitators and results of cuproptosis, respectively. Through copper depletion, glutathione (GSH) blocks the cuproptosis process, rescues the activation of glutamine transporters, and prevents the loss of Fe-S cluster proteins, expect for protecting cancer cells from apoptosis, protein degradation and oxidative damage. Our results are significative for understanding cuproptosis process and developing novel anticancer reagents based on cuproptosis.
2022-11-17 | PXD037278 | Pride
Project description:Wilson disease (WD) is a severe metabolic disorder caused by genetic inactivation of copper-transporting ATPase ATP7B. In WD, copper accumulates in several tissues, particularly in the liver, inducing marked time-dependent pathological changes. To identify initial events in the copper-dependent development of liver pathology we utilized the Atp7b-/- mice, an animal model for WD. Analysis of mRNA from livers of control and Atp7b-/- 6 weeks-old mice using oligonucleotide arrays revealed specific changes of the transcriptome at this stage of copper accumulation. Few messages (29 up-regulated and 46 down-regulated) change their abundance more than 2-fold pointing to the specific effect of copper on gene expression/mRNA stability. The gene ontology analysis revealed copper effects on distinct metabolic pathways. Experiment Overall Design: RNA isolation for microarrays: Immediately after removal, what size [mg] the liver pieces for RNA isolation were frozen in liquid nitrogen and stored till further use. The total RNA was isolated from frozen mouse livers using TRIZOL reagent (Invitrogen) according to manufacturerâs recommendations followed by a subsequent sample
2008-06-13 | E-GEOD-5348 | biostudies-arrayexpress
Project description:Higher plants have developed sophisticated mechanisms to efficiently acquire and use micronutrients such as copper and iron. In the present work, we studied effects produced by the presence of a wide copper range in growth media and altered copper transport on iron homeostasis in Oryza sativa plants. The global analysis of gene expression in the rice seedlings grown under copper deficiency versus excess in the medium showed an increased expression of the genes involved in iron homeostasis. Different iron-related genes are expressed under either copper deficiency and excess, such as those that encode ferredoxin and transcriptional regulator IRON-RELATED TRANSCRIPTION FACTOR 2 (OsIRO2), respectively. As expected, the expression of OsCOPT1, which encodes a high affinity copper transport protein, was up-regulated under copper deficiency, and the expression of OsIRO2 targets were increased under copper excess. Arabidopsis COPT1 overexpression (C1OE) in rice causes root shortening under copper excess, modifies the expression of the putative Fe-sensing factor HEMERYTHRIN MOTIF-CONTAINING REALLY INTERESTING NEW GENE- AND ZINC-FINGER (OsHRZ1) and enhances the expression of OsIRO2 and its targets, which suggests a role of copper in iron signaling. Our studies conducted under simultaneous copper and iron deficiencies indicate that C1OE plants are more sensitive than the wild-type controls to root growth inhibition. The C1OE rice plants grown on soil contained higher endogenous iron concentration in grains than the wild-type plants (both brown and white grains). The results obtained herein showed the interaction between homeostatic networks of iron and copper, and suggest that strategies to obtain crops with optimized nutrient concentrations in edible parts should take into account this interaction.
2017-06-20 | GSE89109 | GEO
Project description:To identify genes which are differentially expressed in Corynebacterium glutamicum in the absence of copper, we performed DNA microarray analyses of cells cultivated under copper starvation conditions compared to copper sufficiency.
2018-08-28 | GSE117530 | GEO