Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1148593 | ENA |
REPOSITORIES: ENA
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Project description:Membrane protection against oxidative damage is tightly buffered by glutathione peroxidase 4 (GPX4), and endogenous radical-trapping antioxidants such as ubiquinone, vitamin E and K. Deficiencies in these protective systems have been linked to the accumulation of phospholipid peroxidation and ferroptosis induction. Recently, ferroptosis suppressor protein 1 (FSP1) was identified as a key player in this process, preventing phospholipid peroxidation and ferroptosis by regenerating radical-trapping antioxidants. Yet, regulators of FSP1 have remained largely unknown, and their identification is critical for understanding the mechanism regulating phospholipid peroxidation and ferroptosis. In this study, we conducted a CRISPR-Cas9 screen to uncover factors influencing FSP1 function, identifying vitamin B2 (riboflavin) as a yet-unaccounted modulator of ferroptosis sensitivity. We demonstrate that vitamin B2, unlike other vitamins that directly act as radical-trapping antioxidants, facilitates the recycling of lipid-soluble antioxidants by directly supporting FSP1 stability and activity, thereby mitigating phospholipid peroxidation. Thus, we uncovered a direct role of vitamin B2 in maintaining membrane integrity and supporting membrane tolerance to lipid peroxidation and ferroptosis resistance. Our findings provide a rational strategy to modulate the FSP1-antioxidant recycling pathway, with potential implications for treating cancer and other diseases where ferroptosis plays a pivotal role.
2025-10-31 | PXD061038 | Pride
Project description:Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. Here, we show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by inactivating the ROS-p53 axis. Because p53 inactivation occurs late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production. There were 3 experimental groups (untreated, NAC-treated and Vitamin E-treated. Each group consisted of 5 animals, and from each animal we harvested 2 tumor samples. Hence, in total 3x10=30 samples were profiled.
2014-01-31 | E-GEOD-52594 | biostudies-arrayexpress
Project description:Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. Here, we show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by inactivating the ROS-p53 axis. Because p53 inactivation occurs late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.
2014-01-31 | GSE52594 | GEO
Project description:To study pathways associated with ferroptosis sensitivity
2022-06-01 | GSE173905 | GEO
Project description:Homeostasis during the perinatal period is critical for the correct development of mammals and unbalances in the redox potential are common in this stage. Thus, enrichment of maternal diets with antioxidants may be useful to improve piglet early development. We have tested the effects of sows’ diet enrichment with different antioxidants on the piglets’ adipose tissue functioning, in comparison to a control diet with a basal antioxidant level, by studying gene expression and cellularity. The maternal diet strongly influenced adipose tissue transcriptome of the offspring post-weaning. Piglets born to sows supplemented with either vitamin E or hydroxytyrosol show improved metabolic and antioxidant status of adipose tissue, while animals from control group show impaired homeostasis and activation of oxidative stress, immune signalling, and inflammation pathways. Moreover, vitamin E, when supplemented alone at a high dose, activated lipid metabolism and increased adipocyte size. When both vitamin E and hydroxytyrosol were combined, the gene expression profile was scarcely affected in comparison to the control, showing a prooxidant/proinflamatory adipose tissue, which is an unexpected result with different potential explanations. Findings deepen in the processes taking place in adipose tissue of genetically fat individuals and highlight the crucial role of antioxidants in fat cells metabolism
2024-09-02 | GSE249774 | GEO
Project description:Suppression of endogenous CBS promotes Ferroptosis
| PRJNA868873 | ENA
Project description:Tocopherols (Vitamin E) are lipophilic antioxidants that are synthesized by all plants and are particularly abundant in seeds. Two tocopherol deficient mutant loci were used to examine how tocopherol deficiency impacts global gene expression during the critical peroid of germination and early seedling development when tocopherols are essential. vte1 lacks all tocopherols, but accumulates the tocopherol pathway intermediate DMPBQ,. vte2 which lacks all tocopherols and pathway intermediates. We used microarrays to examine the global gene expression in early seedlings and identify distinct classes of genes whose expression is affected by tocopherol deficient mutants vte1 and vte2. Keywords: genetic modification
2006-12-29 | GSE4847 | GEO
Project description:African American men are disproportionately affected by both vitamin D deficiency and increased risk of prostate cancer. We used microarrays to quantify gene expression of vitamin D-related genes in the benign epithelium in a diverse group of radical prostatectomy patients
2016-12-09 | GSE91037 | 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