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The biological effect of asbestos exposure is dependent on changes in iron homeostasis
Citation:
Ghio, Andy, J. Soukup, L. Dailey, H. Tong, AND J. Richards. The biological effect of asbestos exposure is dependent on changes in iron homeostasis. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 28(14):698-705, (2016).
Impact/Purpose:
This paper proposes that silicates, such as asbestos, complex iron and disrupt iron homeostasis. Iron is essential for cell survival and accordingly the response by the host cells is focused on correction of the iron homeostasis to one which supports continued survival.
Description:
Abstract Functional groups on the surface of fibrous silicates can complex iron. We tested the postulate that 1) asbestos complexes and sequesters host cell iron resulting in a disruption of metal homeostasis and 2) this loss of essential metal results in an oxidative stress and biological effect in respiratory epithelial cells. Exposure of BEAS-2B cells to 50 μg/mL chrysotile resulted in diminished concentrations of mitochondrial iron. Pre-incubation of these cells with 200 μM ferric ammonium citrate (FAC) prevented significant mitochondrial iron loss following the same exposure. The host response to chrysotile included increased expression of the importer divalent metal transporter-1 (DMT1) supporting a functional iron deficiency. Incubation of BEAS-2B cells with both 200 μM FAC and 50 μg/mL chrysotile was associated with a greater cell accumulation of iron relative to either iron or chrysotile alone reflecting increased import to correct metal deficiency immediately following fiber exposure. Cellular oxidant generation was elevated after chrysotile exposure and this signal was diminished by co-incubation with 200 μM FAC. Similarly, exposure of BEAS-2B cells to 50 µg/mL chrysotile was associated with release of the pro-inflammatory mediators interleukin (IL)-6 and IL-8 and these changes were diminished by co-incubation with 200 μM FAC. We conclude that 1) the biological response following exposure to chrysotile is associated with complexation and sequestration of cell iron and 2) increasing available iron in the cell diminished the effects of asbestos exposure.
