The Science of The Total Environment, Год журнала: 2024, Номер 952, С. 175875 - 175875
Опубликована: Авг. 30, 2024
Язык: Английский
Redox Biology, Год журнала: 2022, Номер 53, С. 102349 - 102349
Опубликована: Май 22, 2022
Humans are inevitably exposed to ethyl carbamate (EC) via consumption of fermented food and beverages. EC, known as an environmental toxin, can cause oxidative stress-mediated severe toxicity, but the underlying mechanisms remain unveiled. Ferroptosis is a newly identified ROS-mediated non-apoptotic cell death characterized by iron accumulation excessive lipid oxidation. In this study, we first found that EC triggered ferroptosis in liver cells detection decreased viability, GSH, GPX4 Ferritin levels, well increased MDA contents. inhibitor ferrostatin-1 (Fer-1) pretreatment rescued ferroptotic damage, indicating was critical for EC-caused death. Furthermore, GSH synthesis precursor N-acetylcysteine displayed significant anti-ferroptotic properties suggested depletion might be main under exposure. EC-triggered mainly depended on suppressed inhibition SLC7A11 GCLC expressions. Notably, blocked Nrf2 activation repression phosphorylation modification nuclear translocation, which further resulted occurrence. We also observed EC-induced dysfunction inflammation, accompanied with stress, downregulated signaling Balb/c mice, could effectively reversed Fer-1 tBHQ pretreatment. Together, our study indicated new mechanism attributed inactivation depletion.
Язык: Английский
Процитировано
142
Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10
Опубликована: Фев. 10, 2022
Ferroptosis, a type of cell death triggered by excessive accumulation iron-dependent lipid peroxidation, possesses an excellent potential in cancer treatment. However, many colorectal (CRC) lines are resistant to ferroptosis induced erastin and RSL3, the classical ferroptotic inducers. Moreover, underlying mechanism resistance remains poorly elucidated. This study sought discover major factor contributing CRC. The findings will help design strategies for triggering application individualized tumor therapy. Here, we show that tetrahydrobiopterin (BH4) determines sensitivity CRC cells erastin. GTP cyclohydrolase-1 (GCH1) is first rate-limiting enzyme BH4. Genetic or pharmacological inhibition GCH1 decreased BH4 assisted induction, peroxidation enhancement, ferrous iron accumulation. supplementation completely inhibited features resulting from knockdown. Unexpectedly, knockdown failed enhance RSL3-induced Mechanistically, drastically activated ferritinophagy during treatment rather than RSL3 Administration autophagy inhibitor reversed GCH1-knockdown cells. co-treatment vivo synergistically growth Overall, our results identified GCH1/BH4 metabolism as burgeoning defense Inhibiting promoted erastin-induced activating ferritinophagy, suggesting combining inhibitors with novel therapeutic strategy.
Язык: Английский
Процитировано
128
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Дек. 10, 2023
Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt
Язык: Английский
Процитировано
72
Cell Death Discovery, Год журнала: 2024, Номер 10(1)
Опубликована: Янв. 24, 2024
Abstract Ferroptosis represents a distinct form of programmed cell death triggered by excessive iron accumulation and lipid peroxidation-induced damage. This mode differentiates from classical in terms morphology biochemistry. stands out for its exceptional biological characteristics has garnered extensive research conversations as death. Its dysfunctional activation is closely linked to the onset diseases, particularly inflammation cancer, making ferroptosis promising avenue combating these conditions. As such, exploring may offer innovative approaches treating cancer inflammatory diseases. Our review provides insights into relevant regulatory mechanisms ferroptosis, examining impact ferroptosis-related factors both physiological pathological perspectives. Describing crosstalk between tumor- inflammation-associated signaling pathways potential inducers overcoming drug-resistant cancers are discussed, aiming inform further novel therapeutic directions relation
Язык: Английский
Процитировано
51
Redox Biology, Год журнала: 2023, Номер 65, С. 102825 - 102825
Опубликована: Июль 25, 2023
Chemotherapeutic agents, such as doxorubicin (DOX), may cause cardiomyopathy, even life-threatening arrhythmias in cancer patients. Ferroptosis-an iron-dependent oxidative form of programmed necrosis, plays a pivotal role DOX-induced cardiomyopathy (DIC). Prostaglandins (PGs) are bioactive signaling molecules that profoundly modulate cardiac performance both physiologic and pathologic conditions. Here, we found PGE2 production its E-prostanoid 1 receptor (EP1) expression were upregulated erastin (a ferroptosis inducer) or DOX-treated cardiomyocytes. EP1 inhibition markedly aggravated cardiomyocyte ferroptosis, whereas activation exerted opposite effect. Genetic depletion cardiomyocytes worsens injury mice, which was efficiently rescued by the inhibitor Ferrostatin-1 (Fer-1). Mechanistically, protected from promoting nuclear factor erythroid 2-related 2 (Nrf2)-driven anti-oxidative gene expression, glutathione peroxidase 4 (GPX4) solute carrier family 7 member 11 (SLC7A11). coupled with Gαq to elicit intracellular Ca2+ flux activate PKC/Nrf2 cascade ferroptotic also prevents human Thus, PGE2/EP1 axis protects activating represent an attractive strategy for DIC prevention treatment.
Язык: Английский
Процитировано
42
Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)
Опубликована: Янв. 18, 2024
Abstract Ferroptosis is a regulatory cell death process pivotal in myocardial ischemia–reperfusion (I/R) injury. However, the precise mechanism underlying ferroptosis remains less known. In this study, we investigated pathophysiological mechanisms of methylmalonic acid (MMA) associated with activation cardiomyocytes after I/R. We found an increase level MMA patients acute injury reperfusion and AC16 cells under hypoxia/reoxygenation (H/R) condition. treatment was to be excessive oxidative stress cardiomyocytes, leading ferroptosis-related mice I/R injury, aggravated ferroptosis, which amplified infarct size cardiac dysfunction. Mechanistically, promoted NOX2/4 expression reactive oxygen species (ROS) production aggravating Notably, increased ROS further activated by inhibiting solute carrier family 7 member 11 (SLC7A11) glutathione peroxidase 4 (GPX4) expression. addition, decreased ectopic nuclear distribution factor E2-related 2 (NRF2) increasing interaction between NRF2 kelch-like ECH-associated protein 1 (KEAP1). This impeded GPX4/SLC7A11, downstream NRF2, activating Collectively, our study indicates that activates generation, induces exacerbate cardiomyocyte model. These findings may provide new perspective for clinical warrant investigation.
Язык: Английский
Процитировано
16
Redox Biology, Год журнала: 2022, Номер 58, С. 102522 - 102522
Опубликована: Окт. 31, 2022
The balance between oxidation and antioxidant is crucial for maintaining homeostasis. Once disrupted, it can lead to various pathological outcomes diseases, such as depression. Oxidative stress result in or aggravate a battery of processes including mitochondrial dysfunction, neuroinflammation, autophagical disorder ferroptosis, which have been found be involved the development Inhibition oxidative related help improve In this regard, nuclear factor erythroid 2-related 2 (Nrf2) defense system may play pivotal role. Nrf2 activation not only regulate expression series genes that reduce its damages, but also directly above combat corresponding alterations. Therefore, targeting has great potential treatment Activation antidepressant effect, specific mechanism remains elucidated. This article reviews key role depression, focusing on possible mechanisms regulating depression treatment. Meanwhile, we summarize some natural synthetic compounds therapy. All provide new insights into broad basis clinical transformation.
Язык: Английский
Процитировано
66
Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)
Опубликована: Окт. 19, 2023
Abstract Immunotherapy has good potential to eradicate tumors in the long term. However, due low immunogenicity of tumor cells, current cancer immunotherapies are not effective. To address this limitation, we constructed a BSA-FA functionalized iron-containing metal-organic framework (TPL@TFBF) that triggers potent systemic anti-tumor immune response by inducing ferroptosis and pyroptosis cells releasing large quantities damage-associated molecular patterns (DAMPs) induce immunogenicity, showing excellent efficacy against melanoma lung metastases vivo. This nanoplatform forms through coordination between tannic acid (TA) Fe 3+ is then loaded with triptolide (TPL), which coated FA-modified BSA. The nanoparticles target FA modification, TPL, TA. reduced 2+ TA, triggering Fenton reaction resulting ROS production. Moreover, TPL increases production intracellular inhibiting expression nuclear factor erythroid-2 related (Nrf2). Such simultaneous amplification induces undergo pyroptosis, amounts DAMPs, stimulate antigen presentation dendritic (DCs) proliferation cytotoxic T lymphocytes (CD4+/CD8 + cells) inhibit metastasis. In addition, combining nanoparticle treatment checkpoint blockade (ICB) further inhibits growth. work provides new strategy for immunotherapy based on various combinations cell death mechanisms.
Язык: Английский
Процитировано
30
Scientific Reports, Год журнала: 2023, Номер 13(1)
Опубликована: Май 31, 2023
Ferroptosis can be induced by inhibiting antioxidant enzymes GPX4 or system Xc-, increased intracellular iron concentrations, and lipid peroxidation. Recently, it has been suggested that ferroptosis an effective way to induce cancer cell death, although the specific relevance mechanism of have not fully elucidated. Here, we investigated anticancer effects inducers erastin RSL3 on non-small lung (NSCLC) cells. death more effectively in NSCLC cells than erastin, with limited cytotoxicity BEAS-2B normal bronchial epithelial The sensitivity was dependent expression levels; effect reversed ferrostatin-1 (a inhibitor) but Z-VAD-FMK, chloroquine, bafilomycin A1, necrostatin-1. promoting peroxidation, elevating LIP concentration ROS level, blocking GSH-to-GSSH conversion through inhibition induction Nrf2/HO1. Furthermore, autophagosomes disrupted formation autolysosomes lysosomal membrane destabilization. knockdown had a similar phenotypes as RSL3. Taken together, RSL3-induced depends regulation GPX4-Nrf2/HO1 These results may useful predicting response well drug resistant
Язык: Английский
Процитировано
28
Cell Death and Disease, Год журнала: 2023, Номер 14(9)
Опубликована: Сен. 22, 2023
Abstract Kidney diseases remain one of the leading causes human death and have placed a heavy burden on medical system. Regulated cell contributes to pathology plethora renal diseases. Recently, with in-depth studies into kidney death, new iron-dependent modality, known as ferroptosis, has been identified attracted considerable attention among researchers in pathogenesis therapeutics treat them. The majority suggest that ferroptosis plays an important role pathologies multiple diseases, such acute injury (AKI), chronic disease, carcinoma. In this review, we summarize recently regulatory molecular mechanisms discuss pathways action various describe protective effect inhibitors against especially AKI. By summarizing prominent roles different progress made studying provide directions strategies for future research summary, ferroptotic factors are potential targets therapeutic intervention alleviate targeting them may lead treatments patients
Язык: Английский
Процитировано
27