Disruption of Iron Homeostasis Sensitizes Pancreatic Cancer to Irreversible Electroporation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Jun Zhao
PROVIDER: PXD063472 | iProX | Wed Apr 30 00:00:00 BST 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Iron–sulfur (Fe–S) clusters play an essential role in plants as protein cofactors mediating diverse electron transfer reactions. Because they can react with oxygen to form reactive oxygen species (ROS) and inflict cellular damage, the biogenesis of Fe–S clusters is highly regulated. A recently discovered group of 2Fe–2S proteins, termed NEET proteins, was proposed to coordinate Fe–S, Fe and ROS homeostasis in mammalian cells. Here we report that disrupting the function of AtNEET, the sole member of the NEET protein family in Arabidopsis thaliana, triggers leaf‐associated Fe–S‐ and Fe‐deficiency responses, elevated Fe content in chloroplasts (1.2–1.5‐fold), chlorosis, structural damage to chloroplasts and a high seedling mortality rate. Our findings suggest that disrupting AtNEET function disrupts the transfer of 2Fe–2S clusters from the chloroplastic 2Fe–2S biogenesis pathway to different cytosolic and chloroplastic Fe–S proteins, as well as to the cytosolic Fe–S biogenesis system, and that uncoupling this process triggers leaf‐associated Fe–S‐ and Fe‐deficiency responses that result in Fe over‐accumulation in chloroplasts and enhanced ROS accumulation. We further show that AtNEET transfers its 2Fe–2S clusters to DRE2, a key protein of the cytosolic Fe–S biogenesis system, and propose that the availability of 2Fe–2S clusters in the chloroplast and cytosol is linked to Fe homeostasis in plants.
2019-12-22 | GSE127300 | GEO
Project description:Iron (Fe) is an essential micronutrient for the survival and proliferation of plants. Plants have evolved complex mechanisms to maintain Fe homeostasis in response of Fe deficiency conditions. To explore the mechanisms of Populus tomentosa response to Fe deficiency, we evaluated the physiological, biochemical and transcriptome differences of P. tomentosa between Fe-sufficient and Fe-deficient conditions. The results showed that, under Fe-free conditions, the chlorophyll synthesis and photosynthesis pathways in shoots were extremely depressed. The inhibition of these pathways caused chlorosis and reduced shoot growth. Meanwhile, although both two photosynthetic systems (PSI and PSII) were inhibited under Fe limited conditions, PSI is affected more serious and earlier than PSII. In order to maintain Fe homeostasis, several genes involved in Fe regulation network were differentially expressed. At the late period of Fe deficiency response, some genes (BTS, bHLH38/39 and PYE) in PYE regulatory network were up-regulated in roots, while some root-specific ethylene-dependent FIT regulatory genes (EIN3, ERF and FIT) were down-regulated. Moreover, FRO2 was induced in P. tomentosa roots to reduce more Fe3+, which is similar with other strategy I plants. It is interest that we found another Fe2+ transporter gene (NRAMP1) was induced, instead of the well-known Fe2+ transporter gene (IRT1) for strategy I plants, to promote Fe2+ absorption at the Fe deficiency late stage.
2020-01-01 | GSE116838 | GEO
Project description:We analyze Global M6A Abundance in PANC-1 cells treated with fisetin by MeRIP-seq
2024-07-02 | GSE179881 | GEO
Project description:To explore the critical non-coding RNAs in the regulation of ferroptosis, we treated panc-1 with cystine depletion.We then performed gene expression profiling analysis using data obtained from RNA-seq of panc-1 cultured normally and panc-1 treated with cystine depletion for 24h in triplicate.
2023-03-10 | GSE216567 | GEO
Project description:To explore the critical non-coding RNAs in the regulation of ferroptosis, we treated panc-1 with cystine depletion.We then performed gene expression profiling analysis using data obtained from RNA-seq of panc-1 cultured normally and panc-1 treated with cystine depletion for 24h in triplicate.
2023-03-10 | GSE216566 | GEO
Project description:To explore the critical non-coding RNAs in the regulation of ferroptosis, we treated panc-1 with cystine depletion.We then performed gene expression profiling analysis using data obtained from RNA-seq of panc-1 cultured normally and panc-1 treated with cystine depletion for 24h in triplicate.
2023-03-10 | GSE216568 | GEO
Project description:Iron and manganese are part of a small group of transition metals required for photosynthetic electron transport. Here, we present evidence for a functional link between iron and manganese homeostasis. In the unicellular cyanobacterium, Synechocystis sp. PCC 6803 Fe and Mn deprivation resulted in distinct modifications of the function of the photosynthetic apparatus. For example, iron limitation modifies the rate of QA re-oxidation in photosystem II, a complex that contains more Mn than Fe. The intracellular elemental quotas of Fe and Mn are also linked. Fe limitation reduces the intracellular Mn quota. Mn limitation did not exert a reciprocal effect on Fe quotas. Microarray analysis comparing Mn and Fe limitation revealed a stark difference in the extent of the transcriptional response to the two limiting conditions, reflective of the physiological data. The effects of Fe limitation on the transcriptional network are widespread while the effects on Mn limitation are highly specific. Our analysis also revealed an overlap in the transcriptional response of specific Fe and Mn transporters. This overlap provides a framework for explaining Fe limitation induced changes in Mn quotas. Fe transporters can serve as a low affinity Mn transport system. Under iron limitation the specificity of the Fe transport system changes, making it a less efficient Mn transport system.
2013-06-29 | GSE48416 | GEO
Project description:To control infection, mammals actively withhold essential nutrients, including the transition metal manganese, by a process termed nutritional immunity. A critical component of this host response is the manganese-chelating protein calprotectin. While many bacterial mechanisms for overcoming nutritional immunity have been identified, the intersection between metal starvation and other essential inorganic nutrients has not been investigated. Here, we report that overexpression of an operon encoding a highly conserved inorganic phosphate importer, PstSCAB, increases the sensitivity of Staphylococcus aureus to calprotectin-mediated manganese sequestration. Further analysis revealed that overexpression of pstSCAB does not disrupt manganese acquisition or result in overaccumulation of phosphate by S. aureus However, it does reduce the ability of S. aureus to grow in phosphate-replete defined medium. Overexpression of pstSCAB does not aberrantly activate the phosphate-responsive two-component system PhoPR, nor was this two-component system required for sensitivity to manganese starvation. In a mouse model of systemic staphylococcal disease, a pstSCAB-overexpressing strain is significantly attenuated compared to wild-type S. aureus This defect is partially reversed in a calprotectin-deficient mouse, in which manganese is more readily available. Given that expression of pstSCAB is regulated by PhoPR, these findings suggest that overactivation of PhoPR would diminish the ability of S. aureus to resist nutritional immunity and cause infection. As PhoPR is also necessary for bacterial virulence, these findings imply that phosphate homeostasis represents a critical regulatory node whose activity must be precisely controlled in order for S. aureus and other pathogens to cause infection.
| S-EPMC7240092 | biostudies-literature
Project description:Iron and manganese are part of a small group of transition metals required for photosynthetic electron transport. Here, we present evidence for a functional link between iron and manganese homeostasis. In the unicellular cyanobacterium, Synechocystis sp. PCC 6803 Fe and Mn deprivation resulted in distinct modifications of the function of the photosynthetic apparatus. For example, iron limitation modifies the rate of QA re-oxidation in photosystem II, a complex that contains more Mn than Fe. The intracellular elemental quotas of Fe and Mn are also linked. Fe limitation reduces the intracellular Mn quota. Mn limitation did not exert a reciprocal effect on Fe quotas. Microarray analysis comparing Mn and Fe limitation revealed a stark difference in the extent of the transcriptional response to the two limiting conditions, reflective of the physiological data. The effects of Fe limitation on the transcriptional network are widespread while the effects on Mn limitation are highly specific. Our analysis also revealed an overlap in the transcriptional response of specific Fe and Mn transporters. This overlap provides a framework for explaining Fe limitation induced changes in Mn quotas. Fe transporters can serve as a low affinity Mn transport system. Under iron limitation the specificity of the Fe transport system changes, making it a less efficient Mn transport system. We monitored the gene expression of Synechocystis PCC6083 at standard conditions and after 2 days of iron limitation (0Fe), manganese limitation (0Mn) and combined iron and manganese limitation (0Fe0Mn). Each timepoint and condition was sampled in triplicates. Due to strong deviations in one of the three repeats for the 0Mn and 0Fe0Mn conditions, the corresponding replicates were excluded from further analysis.
2013-06-29 | E-GEOD-48416 | biostudies-arrayexpress
Project description:Analysis of gene alterations in PANC-1 cells treated with different concentration of Ikarugamycin (Ika). A broad variety of biological activities of IKA has been reported, such as immune regulation, cytotoxic properties, anti-tumor effects and other pharmacological effects. This study provides insight into molecular basis of Ika in pancreatic cancer.
2018-10-02 | GSE120713 | GEO