Biochemical mechanism of erastin-induced ferroptotic cell death in neuronal cells

Hou, Ming-Jie; Wang, Pan; Zhu, Bao Ting

doi:10.3724/abbs.2023058

Cited by 3 publications

(1 citation statement)

References 59 publications

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“…It has been reported that ER-induced GSH depletion activated disulfide isomerase (PDI) which induced iNOS, resulting in accumulation of cellular lipid ROS. Hou et al, have also shown that ER-induced GSH depletion leads to activation of PDI, which then mediates ferroptosis by catalyzing nNOS dimerization, resulting in the accumulation of cellular • NO, ROS and lipid ROS which ultimately causes ferroptotic cell death in immortalized HT22 mouse hippocampal neuronal cells [47]. We have also previously reported that • NO-generating drug, NCX4040, induces ferroptosis in colon cancer cells which was further enhanced in the presence of ER [40].…”

Section: Discussionmentioning

confidence: 66%

Molecular Mechanisms of Erastin-Induced Ferroptosis in Human Ovarian Tumor Cells

Sinha,

Carri,

Brown

et al. 2024

Preprint

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Erastin (ER) induces cell death by utilizing the process of ferroptosis via generation of reactive oxygen species (ROS). Ferroptosis is characterized by accumulation of ROS within the cell, leading to an iron-dependent oxidative damage-mediated cell death. Here, we have examined ferroptosis-dependent mechanism(s) of cytotoxicity of ER in K-RAS mutant human ovarian tumor OVCAR-8 and NCI/ADR-RES cell lines. We used these cell lines to decipher the mechanisms of ER as NCI/ADR-RES cells express higher activities of SOD, glutathione peroxidase and transferases than OVCAR-8 cells. We found that ER was equally cytotoxic to both cells; ER formed more ROS in OVCAR-8 cells than in NIH/ADR-RES cells. Ferrostatin-1, an inhibitor of ferroptosis, inhibited ER-induced cell death in both cell lines. In contrast, RSL3 (RAS-selective lethal 3), an inducer of ferroptosis, significantly enhanced cell death in both cell lines. ER induced significant lipid peroxidation only in OVCAR-8 cells. We found that RSL3 was more cytotoxic to NCI/ADR-RES cells and significantly enhanced ER-induced lipid peroxidation in both cells, indicating GPX4 was involved in the process of ER-mediated ferroptosis. ER treatment also differentially modulated several ferroptosis related genes (e.g., HMOX1/OH1, and CHAC1) in these cells, indicating ER-induced cell death may be mediated differently in OVCAR-8 and NCI/ADR-RES ovarian cells. Our studies suggest that combinations of ER and RSL3 may contribute significantly to the treatment of ovarian cancers, including those that are resistant to other therapeutic agents due to the presence of P-gp or tumors with Ras mutation in the clinic. ER induced ferroptosis may also be an important treatment modality for resistant tumors expressing MDR1 in the clinic.

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Section: Discussionmentioning

confidence: 66%

Molecular Mechanisms of Erastin-Induced Ferroptosis in Human Ovarian Tumor Cells

Sinha,

Carri,

Brown

et al. 2024

Preprint

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Understanding the Mechanism of Ferroptosis in Neurodegenerative Diseases

Ma,

Liu,

Chen

et al. 2024

Front. Biosci. (Landmark Ed)

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Neurodegenerative disorders are typified by the progressive degeneration and subsequent apoptosis of neuronal cells. They encompass a spectrum of conditions, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), epilepsy, brian ischemia, brian injury, and neurodegeneration with brain iron accumulation (NBIA). Despite the considerable heterogeneity in their clinical presentation, pathophysiological underpinning and disease trajectory, a universal feature of these disorders is the functional deterioration of the nervous system concomitant with neuronal apoptosis. Ferroptosis is an iron (Fe)-dependent form of programmed cell death that has been implicated in the pathogenesis of these conditions. It is intricately associated with intracellular Fe metabolism and lipid homeostasis. The accumulation of Fe is observed in a variety of neurodegenerative diseases and has been linked to their etiology and progression, although its precise role in these pathologies has yet to be elucidated. This review aims to elucidate the characteristics and regulatory mechanisms of ferroptosis, its association with neurodegenerative diseases, and recent advances in ferroptosis-targeted therapeutic strategies. Ferroptosis may therefore be a critical area for future research into neurodegenerative diseases.

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Mechanism of RSL3-induced ferroptotic cell death in HT22 cells: crucial role of protein disulfide isomerase

Hou,

Huang,

Zhu

2024

ABBS

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Biochemical mechanism of erastin-induced ferroptotic cell death in neuronal cells

Cited by 3 publications

References 59 publications

Molecular Mechanisms of Erastin-Induced Ferroptosis in Human Ovarian Tumor Cells

Molecular Mechanisms of Erastin-Induced Ferroptosis in Human Ovarian Tumor Cells

Understanding the Mechanism of Ferroptosis in Neurodegenerative Diseases

Mechanism of RSL3-induced ferroptotic cell death in HT22 cells: crucial role of protein disulfide isomerase

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