Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA680497 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13125329.fastq.gz | Fastqsanger.gz | |||
| SRR13125330.fastq.gz | Fastqsanger.gz | |||
| SRR13125331.fastq.gz | Fastqsanger.gz | |||
| SRR13125332.fastq.gz | Fastqsanger.gz | |||
| SRR13125333.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:Ferroptosis is associated with lipid hydroperoxides generated by oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. We identified conjugated linoleates including α-eleostearic acid (αESA) as novel ferroptosis inducers. αESA did not alter GPX4 activity but was incorporated into cellular lipids and promoted lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death was mediated by acyl-CoA synthetase long-chain isoform 1, which promoted αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppressed ferroptosis triggered by αESA but not by GPX4 inhibition. Orally administered tung oil, naturally rich in αESA, limited tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a novel approach to ferroptosis, complementary to GPX4 inhibition, with therapeutic potential.
2021-02-08 | GSE162069 | GEO
Project description:Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.
| S-EPMC8046803 | biostudies-literature
Project description:One of the most critical axes for cell fate determination is how cells respond to excessive reactive oxygen species (ROS)-oxidative stress. Extensive lipid peroxidation commits cells to death via a distinct cell death paradigm termed ferroptosis. However, the molecular mechanism regulating cellular fates to distinct ROS remains incompletely understood. Through siRNA against human receptor-interacting protein kinases (RIPK) family members, we discovered that RIPK4 is crucial for oxidative stress and ferroptotic death. Upon ROS induction, RIPK4 is rapidly activated and the kinase activity of RIPK4 is indispensable to induce cell death. Specific ablation of RIPK4 in kidney proximal tubules protects mice from acute kidney injury induced by cisplatin and renal ischemia/reperfusion. RNA sequencing revealed the dramatically decreased expression of acyl-CoA synthetase medium-chain (ACSM) family members induced by cisplatin treatment which is compromised in RIPK4 deficient mice. Among these ACSM family members, suppression of ACSM1 strongly augments oxidative stress and ferroptotic cell death with induced expression of ACSL4, an important component for ferroptosis execution. Our lipidome analysis revealed that over-expression of ACSM1 leads to the accumulation of monounsaturated fatty acids (MUFAs), attenuation of polyunsaturated fatty acids (PUFAs) production, and thereby cellular resistance to ferroptosis. Hence, knock-down ACSM1 re-sensitizes RIPK4 KO cells to oxidative stress and ferroptotic death. In conclusion, RIPK4 is a key player involved in oxidative stress and ferroptotic death, which is potentially important for a broad spectrum of human pathologies. The link between RIPK4-ASCM1 axis to PUFAs and ferroptosis reveals a novel mechanism to oxidative stress induced necrosis and ferroptosis.
2024-09-04 | GSE276038 | GEO
Project description:To investigate the mechanisms related to anti-ferroptotic effects of red clover extract, we performed differentially expressed genes analysis using data obtained from the RNA-seq of system xCT knockout mouse embryonic fibroblast cells.
2023-12-01 | GSE221119 | GEO
Project description:Adult Wistar rats were fed diet enriched with either α-linolenic acid (ALA) or fish oil for 8 (n=10) weeks. Colitis was induced in rats using 5% dextran sulfate sodium for 7 days. The rats were dissected and RNA was isolated from the colon tissues of rats, the samples from 6 rats were pooled and used for the microarray experiments. Global gene expression analysis was done in duplicates in each group and the results were compared to n-6 fatty acid group. α-linolenic acid (ALA) and fish oil rich in eicosapentaenoic acid and docosahexaenoic acid significantly attenuated the symptoms of colitis, compared to n-6 fatty acid group. Gene expression analysis has revealed that there is no common gene signature in the two groups.
2016-10-12 | GSE76331 | GEO
Project description:Two rapeseed germplasms named YH25005 and R8Q10 that contain 15% to 21% α-linolenic acid (ALA) in the seed fatty acids was developed and high linolenic acid trait is a new goal to improve the nutritional quality. In order to identify the important biological pathways underpinning high/low linolenic acid trait, the transcriptome profiles of the 24-days-old embryos of YH25005 and R8Q10 was compared to that of two low linolenic acid inbred lines named A28 and SW, by using Illumina RNA-seq. We identified 6140, 8830, 9868, and 11846 differential expression genes in pairewise transcriptomic comparison of R8Q10 vs A28, YH25005 vs A28, R8Q10 vs SW, and YH5005 vs SW, respectively. It was found that some key genes related to fatty acid biosynthesis process, including LEC1, TT8, TT12, FAB1, KASII, FUS3, LEC2, FaTA, FATB, FAD7, ABI3, FAD3, KASI, SUA, Lox1 and Lox2, were significantly altered in YH25005 and R8Q10.
2021-11-05 | GSE186952 | GEO
Project description:To investigate ferroptosis-dependent changes in DNA methylation, a genome wide DNA methylation profiling of ferroptotic (RSL3-treated) multiple myeloma cells (MM1S & MM1R) was performed using the 850K MethylationEPIC BeadChip Array. The ferroptotic DNA methylation signature was compared to myeloma cells pre-treated with the ferroptosis inhibitor ferrostatin-1 (FRSL3), which served as a negative control. In total, three biological replicates per treatment per cell line were included.
2021-11-08 | GSE184576 | GEO
Project description:Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. While ferroptosis has been identified as a mechanism for suppressing cancer, its overall physiological significance remains poorly understood. Recent studies have revealed that labile iron and lipid peroxides are released from ferroptotic cells, leading to the propagation of ferroptosis through lipid peroxidation. However, other specific effects of secreted factors derived from ferroptotic cells remain unclear. We constructed a model cell system capable of inducing ferroptosis by re-expressing the transcription factor BACH1, a potent inducer of ferroptosis, in immortalized mouse embryonic fibroblasts (iMEFs). We investigated the impact of the secreted factors from ferroptotic cells with the iMEFs. As a result, we observed that the administration of supernatant media from ferroptotic iMEFs activated proliferation of hepatoma cells and suppressed cellular senescence-like features. This suggested that ferroptotic MEFs secrete anti-senescent substances. Transcriptome analysis of ferroptotic MEFs revealed an increase in the secretion of longevity factor FGF21 in a BACH1-dependent manner. Furthermore, the anti-senescent effects of the supernatant media from these ferroptotic cells were canceled by the knockout of Fgf21. Totally, it is suggested that BACH1 promotes ferroptosis in fibroblasts and contributes to the suppression of cellular senescence in neighboring cells by inducing FGF21 secretion from fibroblasts. It was also discovered that BACH1 not only activates indirectly the transcription of FGF21 by enhancing ferroptotic stress but also increases FGF21 protein level by suppressing the selective autophagic degradation of FGF21 through the transcriptional repression for Sqstm1 and Lamp2a. This represents a dual mechanism of FGF21 upregulation mediated by BACH1, suggesting that BACH1 is a potent inducer of FGF21 expression. It was also found that the BACH1-ferroptosis-FGF21 axis can suppress obesity of mice under high fat diet or short lifespan of progeria mice, closely associated phenotypes with aging. The inhibition of these aging-related phenotypes is considered to be a novel physiological significance of ferroptosis, and BACH1 is considered to function as a longevity gene by promoting ferroptotsis and subsequent FGF21 expression.
2024-06-11 | GSE238147 | GEO
Project description:Necrosis is commonly found in various solid tumors and predicts worse outcome. Chronic ischemia can initiate tumor necrosis, but how the damaged tissue further expands is unclear. Previous studies found that neutrophils associate with necrosis and could contribute to necrosis development in glioblastoma (GBM) by transferring myeloperoxidase (MPO)-containing granules into tumor cells and inducing tumor cell ferroptosis. How the neutrophilic granule transfer occurs is unknown. Here, through an unbiased small molecule screen, we found that statins can inhibit neutrophil-induced tumor cell death by blocking the neutrophilic content transfer into tumor cells. Surprisingly, we found that neutrophils are engulfed by tumor cells before they are fragmented and release the MPO-containing contents in tumor cells. This process involves LC3-associated phagocytosis (LAP) and can be blocked by inhibiting the Vps34-UVRAG-containing PI3K complex. Inhibition of MPO or depletion of Vps34 in an orthotopic xenograft GBM mouse model reduced necrosis formation and allowed tumor-bearing mice to survive longer. Therefore, this study revealed that the neutrophilic granule transfer involves LAP-mediated neutrophil internalization, which then triggers tumor ferroptotic cell death in glioblastoma. Blocking this process may improve prognosis of GBM.
2024-04-29 | GSE263766 | GEO
Project description:The objective is to understand how the transcriptome of dendritic cells changes after the uptake of ferroptotic cells.
2022-06-02 | GSE205069 | GEO