Overlapping role of c-Jun N-terminal kinase (JNK) 1 and 2 in imidazole ketone erastin-induced ferroptosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA983694 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the generation of excess reactive oxygen species (ROS) and lipid peroxidation. However, it remains largely unknown whether signaling pathways, such as the ROS-activated mitogen-activated protein kinase (MAPK) pathways, affect ferroptosis. The c-Jun N-terminal kinase (JNK), a MAPK signaling molecule that plays an essential role in apoptosis, is activated in response to various stimuli, including oxidative stress. In this study, we examined the functional role of JNK in cell death induced by imidazole ketone erastin (IKE), a potent ferroptosis inducer, using gene knockout technology. We found that JNK1/2 double-knockout cells, but not JNK1 or JNK2 single-knockout cells, were much more tolerant to IKE-induced cell death compared to control cells. We further demonstrated that IKE-induced increase in CTH and HMOX1, key genes in ferroptosis, in control cells was substantially suppressed by the depletion of JNK1 and JNK2. These results suggested that JNK1 and JNK2 play an important, overlapping role in ferroptosis. Our findings advance our understanding of the JNK pathway, which could contribute to future pharmacological developments in ferroptosis-related diseases such as cancer and neurodegeneration.
2023-06-19 | GSE234894 | GEO
Project description:Oridonin, as a natural terpenoids isolated from traditional Chinese medicinal herb Rabdosia rubescens, exhibits anticancer activity against multiple cancers with the IC50 ranging from 10 ¦ÌM to 100 ¦ÌM. We observed that SLC7A11 inhibitor Imidazole ketone erastin (1 ¦ÌM) potently increase the anti-proliferative activity of oridonin at low concentrations. Preliminary investigation demonstrated that combination of Imidazole ketone erastin (1 ¦ÌM) and oridonin induced apoptosis and ferroptosis only in a fraction of cells. To explore the synergistic anti-tumor mechanism of combination of oridonin and Imidazole ketone erastin, second-generation transcriptome sequencing(RNA-seq) was utilized to determine the transcriptome change in Hela cells affected by oridonin and Imidazole ketone erastin. PCA analysis showed that the group of oridonin or Imidazole ketone erastin alone located near the control group, while the group of combination gathered far away from the control group, indirectly indicating that combination of oridonin and Imidazole ketone erastin had synergistic biology function.
2023-12-31 | GSE193751 | GEO
Project description:Ferroptosis is a form of regulated cell death that can be induced by inhibition of the cystine-glutamate antiporter, system xc-. Among the existing system xc- inhibitors, imidazole ketone erastin (IKE) is a potent, metabolically stable inhibitor of system xc- and inducer of ferroptosis potentially suitable for in vivo applications. We investigated the pharmacokinetic and pharmacodynamic features of IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model and demonstrated that IKE exerted an antitumor effect by inhibiting system xc-, leading to glutathione depletion, lipid peroxidation, and the induction of ferroptosis biomarkers both in vitro and in vivo. Using untargeted lipidomics and qPCR, we identified distinct features of lipid metabolism in IKE-induced ferroptosis. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a DLBCL xenograft model.
2019-04-17 | MTBLS774 | MetaboLights
Project description:Ferroptosis is a form of regulated cell death that can be induced by inhibition of the cystine-glutamate antiporter, system xc-. Among the existing system xc- inhibitors, imidazole ketone erastin (IKE) is a potent, metabolically stable inhibitor of system xc- and inducer of ferroptosis potentially suitable for in vivo applications. We investigated the pharmacokinetic and pharmacodynamic features of IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model and demonstrated that IKE exerted an antitumor effect by inhibiting system xc-, leading to glutathione depletion, lipid peroxidation, and the induction of ferroptosis biomarkers both in vitro and in vivo. Using untargeted lipidomics and qPCR, we identified distinct features of lipid metabolism in IKE-induced ferroptosis. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a DLBCL xenograft model.
| S-EPMC6525071 | biostudies-literature
Project description:Pyrrole-imidazole polyamides (PIPs) have been shown to inhibit gene expression by interrupting the DNA-protein interface. Human Ectopic viral integration site 1 (EVI1) is an oncogenic transcription factor which plays a key role in many aggressive forms of cancer. We have developed a novel pyrrole–imidazole polyamide, PIP1 targeting the REL/ELK1 binding site in the EVI1 minimal promoter that can significantly repress the expression of EVI1 in MDA-MB-231 cells. Whole-transcriptome analysis revealed that a fraction of EVI1-driven genes were modulated by PIP1.
2014-07-28 | GSE59502 | GEO
Project description:In order to investigate which genes with different expression in prostate cancer(PCa) cells(LNCaP and PC3) after erastin exposure, and identify the essential ferroptosis related genes (FRGs) associated with ferroptosis in PCa cell. 5.0µM erastin was added in cell medium, and we performed gene expression profiling analysis using data obtained from RNA-seq of 12 different cells.
2023-09-12 | GSE232034 | GEO
Project description:Diets characterized by increased blood levels of ketone bodies can protect the brain against a variety of acute and chronic neurological diseases. Moreover, ketone bodies are neuroprotective in many in vitro models of neurological injury. The underlying mechanisms remain unknown however. Recently, we have shown that ketone bodies do not only decrease neuronal injury and death but also protect long-term potentiation in acute hippocampal slices exposed to oxidative stress in the form of exogenous hydrogen peroxide. Elucidating the mechanisms behind the effects of ketone bodies on neuronal survival and function will undoubtedly lead to the development of novel neuroprotective treatments. Our aim is to determine acute changes in gene expression of CA1 pyramidal neurons exposed to various duration of the ketone bodies acetoacetate and beta-hydroxybutyrate. CA1 hippocampal pyramidal neurons exposed to oxidative stress do not display any long-term potention following burst stimulation of Schaffer collaterals. Incubation with the ketone bodies acetoacetate and beta-hydroxybutyrate for at least 20 min prior to hydrogen peroxide application restores long-term potentiation to control levels. We hypothesize that the neuroprotective effects of ketone bodies are mediated by changes in gene expression. Acute hippocampal slices (400 microns in thickness) were obtained from 4 week-old rats and exposed to acetoacetate and beta-hydroxybutyrate (1 mM each) for 1 h and 6 h. A control group was incubated in artificial cerebrospinal fluid only. After treatment, the hippocampal slices were used immediately for RNA isolation. Isolated RNA was sent for analysis. Each sample sent for analysis included tissue from 7 separate animals. Hybridization to an Affymetrix array is being performed 3 times for each experimental condition.
2008-06-15 | E-GEOD-7323 | biostudies-arrayexpress
Project description:Pyrrole-imidazole polyamides (PIPs) have been shown to inhibit gene expression by interrupting the DNA-protein interface. Human Ectopic viral integration site 1 (EVI1) is an oncogenic transcription factor which plays a key role in many aggressive forms of cancer. We have developed a novel pyrroleM-bM-^@M-^Simidazole polyamide, PIP1 targeting the REL/ELK1 binding site in the EVI1 minimal promoter that can significantly repress the expression of EVI1 in MDA-MB-231 cells. Whole-transcriptome analysis revealed that a fraction of EVI1-driven genes were modulated by PIP1. Global expression changes in MDA-MB-231 cells were evaluated after treating the cells with PIP1 and DMSO for 48 hours. The vehicle DMSO is used as a negative control. Each condition is performed in technical replicates.
2014-07-28 | E-GEOD-59502 | biostudies-arrayexpress
Project description:Diets characterized by increased blood levels of ketone bodies can protect the brain against a variety of acute and chronic neurological diseases. Moreover, ketone bodies are neuroprotective in many in vitro models of neurological injury. The underlying mechanisms remain unknown however. Recently, we have shown that ketone bodies do not only decrease neuronal injury and death but also protect long-term potentiation in acute hippocampal slices exposed to oxidative stress in the form of exogenous hydrogen peroxide. Elucidating the mechanisms behind the effects of ketone bodies on neuronal survival and function will undoubtedly lead to the development of novel neuroprotective treatments. Our aim is to determine acute changes in gene expression of CA1 pyramidal neurons exposed to various duration of the ketone bodies acetoacetate and beta-hydroxybutyrate. CA1 hippocampal pyramidal neurons exposed to oxidative stress do not display any long-term potention following burst stimulation of Schaffer collaterals. Incubation with the ketone bodies acetoacetate and beta-hydroxybutyrate for at least 20 min prior to hydrogen peroxide application restores long-term potentiation to control levels. We hypothesize that the neuroprotective effects of ketone bodies are mediated by changes in gene expression. Acute hippocampal slices (400 microns in thickness) were obtained from 4 week-old rats and exposed to acetoacetate and beta-hydroxybutyrate (1 mM each) for 1 h and 6 h. A control group was incubated in artificial cerebrospinal fluid only. After treatment, the hippocampal slices were used immediately for RNA isolation. Isolated RNA was sent for analysis. Each sample sent for analysis included tissue from 7 separate animals. Hybridization to an Affymetrix array is being performed 3 times for each experimental condition. Keywords: dose response
2007-03-20 | GSE7323 | GEO
Project description:We use RNA Sequencing to analyze the potential molecular mechanisms in human pancreatic cancer cell line BxPC3 cells after erastin and vitamin C treatment for 48h.
2021-12-24 | GSE192362 | GEO