Air pollutants disrupt iron homeostasis to impact oxidant generation, biological effects, and tissue injury
Open accessAbstract
Air pollutants cause changes in iron homeostasis through: 1) a capacity of the pollutant, or a metabolite(s), to complex/chelate iron from pivotal sites in the cell or 2) an ability of the pollutant to displace iron from pivotal sites in the cell. Through either pathway of disruption in iron homeostasis, metal previously employed in essential cell processes is sequestered after air pollutant exposure. An absolute or functional cell iron deficiency results. If enough iron is lost or is otherwise not available within the cell, cell death ensues. However, prior to death, exposed cells will attempt to reverse the loss of requisite metal. This response of the cell includes increased expression of metal importers (e.g. divalent metal transporter 1). Oxidant generation after exposure to air pollutants includes superoxide production which functions in ferrireduction necessary for cell iron import. Activation of kinases and phosphatases and transcription factors and increased release of pro-inflammatory mediators also result from a cell iron deficiency, absolute or functional, after exposure to air pollutants. Finally, air pollutant exposure culminates in the development of inflammation and fibrosis which is a tissue response to the iron deficiency challenging cell survival. Following the response of increased expression of importers and ferrireduction, activation of kinases and phosphatases and transcription factors, release of pro-inflammatory mediators, and inflammation and fibrosis, cell iron is altered, and a new metal homeostasis is established. This new metal homeostasis includes increased total iron concentrations in cells with metal now at levels sufficient to meet requirements for continued function.
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Similar to asbestos, these other particles/fibers function to complex iron.
“Similar to asbestos, these other particles/fibers function to complex iron [131].”
From Asbestos and Iron (2023) · cites this paper as [131]
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“Similar to asbestos, these other particles/fibers function to complex iron [131].”
BackgroundSelf-citation
- Authors
- Ghio, A. J., Soukup, J. M., Dailey, L. A., & Madden, M. C.
- Affiliations
- Environmental Protection Agency (US)
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 151
- Pages
- 38-55
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC8274387
- OpenAlex
- W3008120590
- Cited by
- 39
- References
- 27
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 3
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Environmental Protection Agency
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- air pollutants, iron homeostasis, iron deficiency, iron chelation, DMT1, superoxide, oxidative stress, inflammation, fibrosis, tissue damage, pro-inflammatory mediators, transcription factors, kinases and phosphatases, cell death
- MeSH terms
- Air Pollutants, Homeostasis, Iron, Iron Chelating Agents, Oxidants, Particulate Matter
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