Particulate matter induces ferroptosis by accumulating iron and dysregulating the antioxidant system

Park, Minkyung; Cho, Young‐Lai; Choi, Yu-Min; Min, Jeong‐Ki; Park, Young-Jun; Yoon, Sung-Jin; Kim, Daesoo; Son, Mi‐Young; Chung, Sung Min; Lee, Heedoo; Lee, Seon-Jin

doi:10.5483/bmbrep.2022-0139

Cited by 10 publications

(11 citation statements)

References 17 publications

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“…Excessive ROS stimulation can cause different types of cell death depending on its dose, duration, and characteristics of the organism. A previous study reported that PM causes ferroptosis [5], a type of cell death that is primarily dependent on intracellular iron overload and lipid peroxidation signaling and is characterized by ROS accumulation due to iron overload-related lipid peroxidation [6,7]. Our results demonstrated in ammasome activation and ferroptosis induced by PM, especially PM 2.5 that contains extraction ions; these cellular responses were inhibited through suppressed iron accumulation, lipid peroxidation, and ROS production.…”

Section: Discussionsupporting

confidence: 51%

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The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages

Lee,

Park,

Park

et al. 2023

Preprint

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Particulate matter (PM) is a global environmental hazard, which affects human health through free radical production, cell death induction, and immune responses. PM activates inflammasomes leading to an excessive inflammatory response, and induces ferroptosis, a type of cell death. Despite ongoing research on the correlation among PM-induced ferroptosis, immune response, and inflammasomes, the underlying mechanism of this relationship has not been elucidated. In this study, we demonstrated the levels of PM-induced cell death and immune responses in murine macrophages, J774A.1 and RAW264.7, depending on the size and composition of particulate matter. PM2.5, with extraction ions, induced significant levels of cell death and immune responses; it induces lipid peroxidation, iron accumulation, and reactive oxygen species (ROS) production, which characterize ferroptosis. In addition, inflammasome-mediated cell death occurred owing to the excessive activation of inflammatory responses. PM-induced iron accumulation activates ferroptosis and inflammasome formation through ROS production; similar results were observed in vivo. These results suggest that the link between ferroptosis and inflammasome formation induced by PM, especially PM2.5 with extraction ions, is established through the iron-ROS axis. Moreover, this study can effectively facilitate the development of a new therapeutic strategy for PM-induced immune and respiratory diseases.

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Section: Discussionsupporting

confidence: 51%

“…PM activates the in ammatory pathway through reactive oxygen species (ROS)-mediated mechanisms [3]. In addition, PM causes oxidative stress, lipid peroxidation, expression of in ammatory cytokine genes, and several types of cell death including ferroptosis [4,5].…”

Section: Introductionmentioning

confidence: 99%

The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages

Lee,

Park,

Park

et al. 2023

Preprint

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“…Calu‐3 cells (2 × 10 6 cells/mouse) and 50% Matrigel (PBS/Matrigel, 1:1 v / v ; BD Biosciences) were mixed and subcutaneously transplanted into the right flank of 4‐week‐old female NRGA mice 21,22 . When the tumor size reached about 100 mm 3 , the mice ( n = 3, per group) were intratumorally injected with SARS‐CoV‐2 Delta (1 × 10 5 pfu/mouse).…”

Section: Methodsmentioning

confidence: 99%

A mouse xenograft long‐term replication yields a SARS‐CoV‐2 Delta mutant with increased lethality

Kim,

Kim

et al. 2024

Journal of Medical Virology

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We recently established a long‐term SARS‐CoV‐2 infection model using lung‐cancer xenograft mice and identified mutations that arose in the SARS‐CoV‐2 genome during long‐term propagation. Here, we applied our model to the SARS‐CoV‐2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS‐CoV‐2. We observed limited mutations in SARS‐CoV‐2 Delta during long‐term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta‐10 and Delta‐12, with both predominant mutations and some additional mutations. Delta‐10 and Delta‐12 showed lower replication capacity compared with SARS‐CoV‐2 Delta in cultured cells; however, Delta‐12 was more lethal in K18‐hACE2 mice compared with SARS‐CoV‐2 Delta and Delta‐10. Mice infected with Delta‐12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta‐12 was associated with lung and brain pathology. Our long‐term infection model can provide mutant viruses derived from SARS‐CoV‐2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.

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“…For instance, Park et al demonstrated the cytotoxic effects of PM 2.5 on small intestine cells. 92 PM 2.5 with extraction ion (EI) components was found to be more cytotoxic than PM 2.5 containing only PAHs, and the cell death mechanism involved ferroptosis, as evidenced by iron overloading, ROS generation, and lipid peroxidation. Liproxstatin-1 and deferiprone attenuated the cytotoxicity induced by PM 2.5 EI.…”

Section: Airborne Particulate Matter (Pm)mentioning

confidence: 99%

“…Several studies have investigated the cytotoxic effects of PM and its association with ferroptosis in different cell types and organs. For instance, Park et al demonstrated the cytotoxic effects of PM 2.5 on small intestine cells . PM 2.5 with extraction ion (EI) components was found to be more cytotoxic than PM 2.5 containing only PAHs, and the cell death mechanism involved ferroptosis, as evidenced by iron overloading, ROS generation, and lipid peroxidation.…”

Section: Ferroptosis Inducers In Environmental Pollutantsmentioning

confidence: 99%

Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

Yang,

Cai,

2024

Environ. Sci. Technol.

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Environmental pollutants have been recognized for their ability to induce various adverse outcomes in both the environment and human health, including inflammation, apoptosis, necrosis, pyroptosis, and autophagy. Understanding these biological mechanisms has played a crucial role in risk assessment and management efforts. However, the recent identification of ferroptosis as a form of programmed cell death has emerged as a critical mechanism underlying pollutant-induced toxicity. Numerous studies have demonstrated that fine particulates, heavy metals, and organic substances can trigger ferroptosis, which is closely intertwined with lipid, iron, and amino acid metabolism. Given the growing evidence linking ferroptosis to severe diseases such as heart failure, chronic obstructive pulmonary disease, liver injury, Parkinson's disease, Alzheimer's disease, and cancer, it is imperative to investigate the role of pollutant-induced ferroptosis. In this review, we comprehensively analyze various pollutant-induced ferroptosis pathways and intricate signaling molecules and elucidate their integration into the driving and braking axes. Furthermore, we discuss the potential hazards associated with pollutant-induced ferroptosis in various organs and four representative animal models. Finally, we provide an outlook on future research directions and strategies aimed at preventing pollutant-induced ferroptosis. By enhancing our understanding of this novel form of cell death and developing effective preventive measures, we can mitigate the adverse effects of environmental pollutants and safeguard human and environmental health.

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Particulate matter induces ferroptosis by accumulating iron and dysregulating the antioxidant system

Cited by 10 publications

References 17 publications

The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages

The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages

A mouse xenograft long‐term replication yields a SARS‐CoV‐2 Delta mutant with increased lethality

Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

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