Air pollutants disrupt iron homeostasis to impact oxidant generation, biological effects, and tissue injury

• Published in: Free radical biology & medicine Vol. 151; pp. 38 - 55
• Main Authors: Ghio, Andrew J., Soukup, Joleen M., Dailey, Lisa A., Madden, Michael C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2020
• Subjects: Air pollution; Iron; Oxidants; Ozone; Particulate matter; Air pollution; Ozone; Iron; Oxidants; Particulate matter
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.02.007

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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•Air pollutant exposures change cell iron homeostasis.•The pollutant, or a metabolite(s), complexes/chelates from the cell.•Alternatively, the pollutant displaces iron from the cell.•An absolute or functional cell iron deficiency results.•Biological effect of the pollutant results from a cell iron deficiency.