MRNA and lncRNA expression profiling analysis in A549 cells treated with DMSO, RSL3 alone, or co-treated with Fer-1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE247883 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:Ferroptotic cell death is dependent on unrestricted lipid peroxidation rather than activation of apoptotic effector caspases. A large number of ferroptosis activators have been reported recently. We used gene sequencing to analyze the effects of four ferroptosis activators (RSL3, N6F11, Fin56 and Erastin) on global gene expression in human PDAC1 cell line.
2023-10-18 | E-MTAB-12241 | biostudies-arrayexpress
Project description:Acquired and primary therapy resistance remain a major hurdle in clinical treatment of multiple myeloma (MM). Despite the availability of broad spectrum anti-cancer drugs, most MM patients eventually relapse and become refractory to current treatments. Therefore, we explored whether therapy-resistant MM cells are sensitive to ferroptosis induction, an iron-catalyzed mode of cell death associated with increased lipid peroxidation. In this study, we exposed glucocorticoid-resistant MM1R and glucocorticoid-sensitive MM1S cells to ferroptosis inducers RSL3 and evaluated their transcriptional changes via RNA sequencing. Compared to untreated controls, ferroptotic RSL3-treated cells displayed a significant upregulation of genes involved in inflammation, kinase signaling, cellular stress, and cell death pathways. Pre-treatment with ferroptosis inhibitor Fer-1 partly reverted these RSL3-induced transcriptional changes and revealed that especially genes involved in metal binding, nuclear receptor signaling, chromatin remodeling, and gene transcription regulation are pivotal for ferroptosis induction. Overall, these findings suggest that ferroptosis effectively targets MM1 cells and that RSL3-mediated ferroptosis triggers similar oxidative stress and cell death pathways in both MM1R and MM1S cells, irrespective of their glucocorticoid-sensitivity status.
2021-11-08 | GSE182638 | GEO
Project description:Ferroptosis is a form of regulated cell death driven by lipid peroxidation of polyunsaturated fatty acids (PUFAs). Endogenous PUFAs are nonconjugated PUFAs and their peroxidation proceeds via the hydrogen-atom transfer (HAT) mechanism. We previously reported that lipids with conjugated double bonds undergo lipid peroxidation mostly via a different mechanism, peroxyl radical addition (PRA), and were much more readily oxidizable than nonconjugated ones. In this study, we aim to elucidate the effects of various unsaturated lipids in sensitizing ferroptosis. We found that while some peroxidation-reactive lipids, such as 7-dehydrocholesterol, vitamins D3 and A, and coenzyme Q10, suppress ferroptosis, both nonconjugated and conjugated PUFAs enhanced cell death induced by RSL3, a ferroptosis inducer. Importantly, we showed that conjugated linolenic acid (CLA 18:3) could act as a ferroptosis inducer by itself and conjugated linoleic acid (CLA 18:2) was more potent in sensitizing cells to RSL3-induced cell death than any nonconjugated PUFAs. We next sought to elucidate the mechanism underlying the different ferroptosis-inducing potency of conjugated and nonconjugated PUFAs. Lipidomics revealed that conjugated and nonconjugated PUFAs are incorporated into distinct cellular lipid species. Furthermore, the different peroxidation mechanisms predict the formation of higher levels of reactive electrophilic aldehydes from conjugated PUFAs than nonconjugated PUFAs, which was confirmed by aldehyde-trapping and mass spectrometry. RNA sequencing revealed that protein processing in the endoplasmic reticulum and proteasome are among the most significantly upregulated pathways in cells treated with CLA 18:3, suggesting increased ER stress and activation of unfolded protein response. Significantly, using click chemistry, we observed increased protein adduction by oxidized lipids in cells treated with an alkynylated CLA 18:2 probe. These results suggest that protein damage by lipid electrophiles is a key step in ferroptosis.
2023-04-17 | GSE224249 | GEO
Project description:Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.
2023-03-02 | PXD039476 | Pride
Project description:In this study, we investigated the potential effect of CYGB on the cellular sensitivity towards (1S, 3R)-RAS-selective lethal small molecule (RSL3)-mediated ferroptosis in the G361 melanoma cells with abundant endogenous expression. Our findings show that an increased basal ROS level and higher degree of lipid peroxidation upon RSL3 treatment contributes to the increased sensitivity of CYGB knockdown G361 cells to ferroptosis. Furthermore, transcriptome analysis demonstrates the enrichment of multiple cancer malignancy pathways upon CYGB knockdown, supporting a tumor suppressive role for CYGB. Remarkably, CYGB knockdown also triggered activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and subsequent induction of pyroptosis target genes. Altogether, we show that silencing of CYGB expression modulates cancer therapy sensitivity via modulation of ferroptosis and pyroptosis cell death signalling pathways.
2022-07-29 | GSE209775 | GEO
Project description:To identify changes in gene expression in daf-16 mutants, we compared expression in fer-15 young adults to expression in fer-15(b26); daf-16(m26) young adults grown at 25?C. At Stanford University, four samples of fer-15 and five samples of fer-15; daf-16 animals were prepared. At the University of Colorado, seven samples of fer-15 and six samples of fer-15; daf-16 was prepared. Set of arrays that are part of repeated experiments Place of growth: At Stanford vs Colorado Genotype: mutant strains vs wt (N2) mixed stage; some expts are reverse dye (wt in channel 2) Biological Replicate Computed
2008-07-29 | E-GEOD-12167 | biostudies-arrayexpress
Project description:To identify changes in gene expression in daf-16 mutants, we compared expression in fer-15 young adults to expression in fer-15(b26); daf-16(m26) young adults grown at 25?C. At Stanford University, four samples of fer-15 and five samples of fer-15; daf-16 animals were prepared. At the University of Colorado, seven samples of fer-15 and six samples of fer-15; daf-16 was prepared. Set of arrays that are part of repeated experiments Place of growth: At Stanford vs Colorado Genotype: mutant strains vs wt (N2) mixed stage; some expts are reverse dye (wt in channel 2)
2008-07-29 | GSE12167 | GEO
Project description:To identify changes in gene expression in age-1 mutants, we compared expression in fer-15(b26) animals to expression in fer-15(b26); age-1(hx542) mutants. We prepared RNA from young adult fer-15(b26) mutants grown at 25?C (five samples prepared at Stanford University and six samples prepared at the University of Colorado) and young adult fer-15(b26); age-1(hx542) mutants (four samples at Stanford University and six samples at the University of Colorado). Set of arrays that are part of repeated experiments Place of growth: Stanford vs Colorado Genotype: mutant strains vs wt (N2) mixed stage; some expts are reverse dye Biological Replicate Computed
2008-07-29 | E-GEOD-12166 | biostudies-arrayexpress
Project description:Smooth muscle cell (SMC) loss is the characteristic feature in the pathogenesis of aortic dissection (AD), and ferroptosis is a novel iron-dependent regulated cell death driven by the excessive lipid peroxidation accumula_x0002_tion. However, whether targeting ferroptosis is an effective approach for SMC loss and AD treatment remains unclear. Here, we found that the iron level, ferroptosis-related molecules TFR, HOMX1, ferritin and the lipid peroxidation product 4-hydroxynonenal were increased in the aorta of AD. Then, we screened several inhibitors of histone methyltransferases and found that BRD4770 had a protective effect on cystine deprivation-, imidazole ketone erastin- or RSL3-induced ferroptosis of SMCs. The classic ferroptosis pathways, System Xc--GPX4, FSP1- CoQ10 and GCH1-BH4 pathways which were inhibited by ferroptosis inducers, were re-activated by BRD4770 via inhibiting mono-, di- and tri- methylated histone H3 at lysine 9 (H3K9me1/2/3). RNA-sequencing analysis revealed that there was a positive feedback regulation between ferroptosis and inflammatory response, and BRD4770 can reverse the effects of inflammation activation on ferroptosis. More importantly, treatment with BRD4770 attenuated aortic dilation and decreased morbidity and mortality in a β-Aminopropionitrile monofumarate-induced mouse AD model via inhibiting the inflammatory response, lipid peroxidation and fer_x0002_roptosis. Taken together, our findings demonstrate that ferroptosis is a novel and critical pathological mechanism that is involved in SMC loss and AD development. BRD4770 is a novel ferroptosis inhibitor and has equivalent protective effect to Ferrostatin-1 at the optimal concentration. Translating insights into the anti-ferroptosis ef_x0002_fects of BRD4770 may reveal a potential therapeutic approach for targeting SMC ferroptosis in AD.
2024-07-16 | GSE272018 | GEO
Project description:To identify changes in gene expression in age-1 mutants, we compared expression in fer-15(b26) animals to expression in fer-15(b26); age-1(hx542) mutants. We prepared RNA from young adult fer-15(b26) mutants grown at 25?C (five samples prepared at Stanford University and six samples prepared at the University of Colorado) and young adult fer-15(b26); age-1(hx542) mutants (four samples at Stanford University and six samples at the University of Colorado). Set of arrays that are part of repeated experiments Place of growth: Stanford vs Colorado Genotype: mutant strains vs wt (N2) mixed stage; some expts are reverse dye
2008-07-29 | GSE12166 | GEO