Acrylamide induces ferroptosis in HSC-T6 cells by causing antioxidant imbalance of the XCT-GSH-GPX4 signaling and mitochondrial dysfunction

Yuan, Yuan; Li, Yucai; Lü, Li; Liu, Hui; Pang, Yong; Yan, Haiyang

doi:10.1016/j.toxlet.2022.08.007

Cited by 24 publications

(13 citation statements)

References 47 publications

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“…Previous studies have considered ferroptosis as an important contributor to ACR toxicity. 25 Similarly, our RNA-seq analysis showed that QCT downregulated the ferroptosis pathway in ACR-exposed HepG2 cells. To identify whether QCT protects against ACR-induced hepatotoxicity by inhibiting ferroptosis, the contents of GSH and MDA, and the protein levels of GPX4 were assessed.…”

Section: Qct Protected Against Acr-induced Liver Injury In Vivo and I...mentioning

confidence: 60%

“…Previous studies have considered ferroptosis as an important contributor to ACR toxicity . Similarly, our RNA-seq analysis showed that QCT downregulated the ferroptosis pathway in ACR-exposed HepG2 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Yuan has indicated that ACR induces ferroptosis in Hepatic stellate cells. 25 It has also been reported that QCT inhibits the ferroptosis pathway to alleviate kainic acid-induced seizure. 39 Hence, it could be suggested that ferroptosis was closely involved in the protective effects of QCT on liver injury caused by ACR.…”

Section: ■ Discussionmentioning

confidence: 99%

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Quercetin Alleviates Acrylamide-Induced Liver Injury by Inhibiting Autophagy-Dependent Ferroptosis

Huang

Zhang

Wang

et al. 2023

J. Agric. Food Chem.

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Acrylamide (ACR) generated in carbohydrate-rich foods during thermal processing has been demonstrated to exhibit hepatotoxicity. As one of the most consumed flavonoids with diet, quercetin (QCT) possesses the ability to protect against ACRinduced toxicity, albeit its mechanism is unclear. Herein, we discovered that QCT alleviated ACR-induced elevated levels of reactive oxygen species (ROS), AST, and ALT in mice. RNA-seq analysis revealed that QCT reversed the ferroptosis signaling pathway upregulated by ACR. Subsequently, experiments indicated that QCT inhibited ACR-induced ferroptosis through the reduction of oxidative stress. With autophagy inhibitor chloroquine, we further confirmed that QCT suppressed ACR-induced ferroptosis by inhibiting oxidative stress-driven autophagy. Additionally, QCT specifically reacted with autophagic cargo receptor NCOA4, blocked the degradation of iron storage protein FTH1, and eventually downregulated the intracellular iron levels and the consequent ferroptosis. Collectively, our results presented a unique approach to alleviate ACR-induced liver injury by targeting ferroptosis with QCT.

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Section: Qct Protected Against Acr-induced Liver Injury In Vivo and I...mentioning

confidence: 60%

Section: Resultsmentioning

confidence: 99%

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Quercetin Alleviates Acrylamide-Induced Liver Injury by Inhibiting Autophagy-Dependent Ferroptosis

Huang

Zhang

Wang

et al. 2023

J. Agric. Food Chem.

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“…Cysteine, mainly derived from extracellular cystine after entering the cell and being reduced, is present in the lowest concentration in the cell, making it the critical rate-limiting factor for the de novo synthesis of GSH. The cystine/glutamate antiporter (system X C – ) on the cell membrane transports the extracellular cysteine into the cell in a 1:1 form while transporting out the intracellular glutamate ( Yuan Y. et al, 2022 ). The system X C – on the cell membrane is a heterodimer consisting of the substrate-specific subunit SLC7A11 (xCT) and the regulatory subunit SLC3A2 ( Koppula et al, 2021 ).…”

Section: Essential Characteristics and Mechanisms Of Ferroptosismentioning

confidence: 99%

Elucidating the progress and impact of ferroptosis in hemorrhagic stroke

Pan

Ding

et al. 2023

Front. Cell. Neurosci.

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Hemorrhagic stroke is a devastating cerebrovascular disease with high morbidity and mortality, for which effective therapies are currently unavailable. Based on different bleeding sites, hemorrhagic stroke can be generally divided into intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), whose pathogenesis share some similarity. Ferroptosis is a recently defined programmed cell deaths (PCDs), which is a critical supplement to the hypothesis on the mechanism of nervous system injury after hemorrhagic stroke. Ferroptosis is characterized by distinctive morphological changes of mitochondria and iron-dependent accumulation of lipid peroxides. Moreover, scientists have successfully demonstrated the involvement of ferroptosis in animal models of ICH and SAH, indicating that ferroptosis is a promising target for hemorrhagic stroke therapy. However, the studies on ferroptosis still faces a serious of technical and theoretical challenges. This review systematically elaborates the role of ferroptosis in the pathogenesis of hemorrhagic stroke and puts forward some opinions on the dilemma of ferroptosis research.

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“…Docking parameters were set to default values. [15] On the basis of the docking fraction results of kirenol with protein and the ligand-protein non-bond interaction force, the docking results for the kirenol derivatives with five proteins [LOX (PDB: 1JNQ), iNOS (PDB: 1M9T), COX-2 (PDB: 1CX2), MMP-8 (PDB: 1A85) and MMP-9 (PDB: 4H3X)] were selected for further investigation and discussion.…”

Section: Molecular Docking Simulationmentioning

confidence: 99%

Design, Synthesis, and Evaluation of Kirenol Derivatives as MMP‐8 Inhibitors with Anti‐inflammatory Activity

Zhao

Liu

et al. 2023

ChemistrySelect

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The diterpene kirenol has notable biological activity. In this study, molecular docking software (Discovery Studio) was adopted to investigate the anti‐inflammatory and antioxidant properties of kirenol. Twenty‐nine kirenol derivatives were synthesized based on the molecular docking outcomes. Cytotoxicity analyses of the kirenol derivatives were performed in Raw264.7 macrophages using the CCK‐8 assay, and nitric oxide (NO) concentrations were determined using the Griess assay. The DCFH‐DA approach identified the general pattern of reactive oxygen species (ROS) fluctuations. The mitochondrial mass and morphology were detected using the Mito‐Tracker Red fluorescent probe. Preliminary bioassay tests indicated that the concentration of NO was substantially reduced by certain derivatives. Moreover, these derivatives inhibited LPS‐induced ROS generation, and one of them exhibited a further reducing ROS generation and pro‐inflammatory response by suppressing excessive mitochondrial fission. These findings suggest that this particular derivative may be a promising natural compound for combating oxidative inflammatory diseases.

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Acrylamide induces ferroptosis in HSC-T6 cells by causing antioxidant imbalance of the XCT-GSH-GPX4 signaling and mitochondrial dysfunction

Cited by 24 publications

References 47 publications

Quercetin Alleviates Acrylamide-Induced Liver Injury by Inhibiting Autophagy-Dependent Ferroptosis

Quercetin Alleviates Acrylamide-Induced Liver Injury by Inhibiting Autophagy-Dependent Ferroptosis

Elucidating the progress and impact of ferroptosis in hemorrhagic stroke

Design, Synthesis, and Evaluation of Kirenol Derivatives as MMP‐8 Inhibitors with Anti‐inflammatory Activity

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