“…GSH, as the main free radical scavenger in cells, maintains biosynthesis from three amino acids, Cys), glycine, and glutamate, and resists ferroptosis progression and lipid peroxidation ( 50 ). Glutathione peroxidase 4 (GPX4) is an antioxidant enzyme containing selenocysteine (Ser) that uses GSH as a substrate to catalyze the reduction of PLOOH to non-toxic PLs-alcohol (PL-OH) and prevent the occurrence of ferroptosis using its unique catalytic ability ( 51 , 52 ).…”
In the last decade, ferroptosis has received much attention from the scientific research community. It differs from other modes of cell death at the morphological, biochemical, and genetic levels. Ferroptosis is mainly characterized by non-apoptotic iron-dependent cell death caused by iron-dependent lipid peroxide excess and is accompanied by abnormal iron metabolism and oxidative stress. In recent years, more and more studies have shown that ferroptosis is closely related to the occurrence and development of lung diseases. COPD, asthma, lung injury, lung fibrosis, lung cancer, lung infection and other respiratory diseases have become the third most common chronic diseases worldwide, bringing serious economic and psychological burden to people around the world. However, the exact mechanism by which ferroptosis is involved in the development and progression of lung diseases has not been fully revealed. In this manuscript, we describe the mechanism of ferroptosis, targeting of ferroptosis related signaling pathways and proteins, summarize the relationship between ferroptosis and respiratory diseases, and explore the intervention and targeted therapy of ferroptosis for respiratory diseases.
“…GSH, as the main free radical scavenger in cells, maintains biosynthesis from three amino acids, Cys), glycine, and glutamate, and resists ferroptosis progression and lipid peroxidation ( 50 ). Glutathione peroxidase 4 (GPX4) is an antioxidant enzyme containing selenocysteine (Ser) that uses GSH as a substrate to catalyze the reduction of PLOOH to non-toxic PLs-alcohol (PL-OH) and prevent the occurrence of ferroptosis using its unique catalytic ability ( 51 , 52 ).…”
In the last decade, ferroptosis has received much attention from the scientific research community. It differs from other modes of cell death at the morphological, biochemical, and genetic levels. Ferroptosis is mainly characterized by non-apoptotic iron-dependent cell death caused by iron-dependent lipid peroxide excess and is accompanied by abnormal iron metabolism and oxidative stress. In recent years, more and more studies have shown that ferroptosis is closely related to the occurrence and development of lung diseases. COPD, asthma, lung injury, lung fibrosis, lung cancer, lung infection and other respiratory diseases have become the third most common chronic diseases worldwide, bringing serious economic and psychological burden to people around the world. However, the exact mechanism by which ferroptosis is involved in the development and progression of lung diseases has not been fully revealed. In this manuscript, we describe the mechanism of ferroptosis, targeting of ferroptosis related signaling pathways and proteins, summarize the relationship between ferroptosis and respiratory diseases, and explore the intervention and targeted therapy of ferroptosis for respiratory diseases.
“… 464 Toxin -mediated Hepatic toxicity Phosphorylation Nrf2 Glyphosate triggers ferroptosis in hepatocyte through suppressing Nrf2 via blocking the phosphorylation and nuclear translocation of Nrf2, resulting in GSH depletion and inhibition of GPX4. 465 BRD7 bromodomain-containing protein 7, GCN5L1 mitochondrial general control of amino acid synthesis 5 like 1, Ptgs2 prostaglandin-endoperoxide synthase 2, LOXs lipoxygenases, TfR1 transferrin receptor 1, NETs neutrophil extracellular traps, IRI ischemia/reperfusion injury, TMEM16A transmembrane member 16A Fig. 8 Epigenetic and posttranslational modification of ferroptosis in Liver diseases and Lung diseases.…”
Section: Epigenetic and Posttranslational Modifications Regulating Fe...mentioning
confidence: 99%
“… 464 Glyphosate triggers ferroptosis in hepatocytes by suppressing Nrf2 via blockade of Nrf2 phosphorylation and nuclear translocation, resulting in GSH depletion and inhibition of GPX4. 465 …”
Section: Epigenetic and Posttranslational Modifications Regulating Fe...mentioning
confidence: 99%
“… 595 Toxin -mediated hepatic toxicity Fer-1 and tBHQ Phosphorylation Nrf2 Ethyl carbamate-induced liver dysfunction and inflammation, accompanied with oxidative stress, ferroptosis and downregulated Nrf2 signaling in Balb/c mice, which could be effectively reversed by Fer-1 and tBHQ pretreatment. 464 Toxin -mediated hepatic toxicity Fer-1 or tBHQ Phosphorylation Nrf2 Fer-1 or tBHQ inhibit Glyphosate triggered ferroptosis-induced liver damage in a mouse mode 465 Acute liver failure AGK2 Phosphorylation MFN2/GPX4 AGK2 inhibits thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway. 596 Acute lung injury MitoQ Phosphorylation - MitoQ pretreatment countered As-induced pulmonary ferroptosis and ALI.…”
Section: Modulation Of Epigenetic and Posttranslational Modifications...mentioning
confidence: 99%
“… 464 Ferrostatin-1 and tBHQ were also found to attenuate liver damage resulting from glyphosate-triggered ferroptosis in a mouse model. 465 …”
Section: Modulation Of Epigenetic and Posttranslational Modifications...mentioning
Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other cell death modes, plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications and posttranslational modifications (PTMs) promote anticancer drug resistance, cancer progression, and metastasis. Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases (NSDs), cardiovascular diseases (CVDs), liver diseases, lung diseases, and kidney diseases. In this review, we first summarize the core molecular mechanisms of ferroptosis. Then, the roles of epigenetic processes, including histone PTMs, DNA methylation, and noncoding RNA regulation and PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, methylation, and ADP-ribosylation, are concisely discussed. The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases, including cancers, NSD, CVDs, liver diseases, lung diseases, and kidney diseases, as well as the application of epigenetic and PTM modulators in the therapy of these diseases, are then discussed in detail. Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases. In addition, these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.
T‐2 toxin is a trichothecene mycotoxin and is considered as an extremely inevitable pollutant with potent hepatotoxicity. However, the approach to alleviation of T‐2 toxin‐triggered hepatotoxicity has been recognized as a serious challenge. Resveratrol (Res) is a polyphenol natural product isolated from various plant species, but its protective effect against T‐2 toxin hepatotoxicity and detailed mechanism remains obscure. In the present study, the effect of Res against the hepatotoxicity was evaluated, and the underlying mechanisms were further revealed in mice. Functionally, Res inhibited liver injury, oxidative damage, and mitochondrial dysfunction induced by T‐2 toxin. Mechanistically, Res modulated Nrf2‐mediated antioxidant pathway and glutathione synthesis inhibition. Collectively, our findings first showed beyond doubt that Res ameliorated T‐2 toxin‐triggered liver injury by regulating Nrf2 pathways in mice.
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