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Sequestration of mitochondrial iron by silica particle initiates a biological effect.

Publication ,  Journal Article
Ghio, AJ; Tong, H; Soukup, JM; Dailey, LA; Cheng, W-Y; Samet, JM; Kesic, MJ; Bromberg, PA; Turi, JL; Upadhyay, D; Scott Budinger, GR; Mutlu, GM
Published in: Am J Physiol Lung Cell Mol Physiol
November 15, 2013

Inhalation of particulate matter has presented a challenge to human health for thousands of years. The underlying mechanism for biological effect following particle exposure is incompletely understood. We tested the postulate that particle sequestration of cell and mitochondrial iron is a pivotal event mediating oxidant generation and biological effect. In vitro exposure of human bronchial epithelial cells to silica reduced intracellular iron, which resulted in increases in both the importer divalent metal transporter 1 expression and metal uptake. Diminished mitochondrial (57)Fe concentrations following silica exposure confirmed particle sequestration of cell iron. Preincubation of cells with excess ferric ammonium citrate increased cell, nuclear, and mitochondrial metal concentrations and prevented significant iron loss from mitochondria following silica exposure. Cell and mitochondrial oxidant generation increased after silica incubation, but pretreatment with iron diminished this generation of reactive oxygen species. Silica exposure activated MAP kinases (ERK and p38) and altered the expression of transcription factors (nF-κB and NF-E2-related factor 2), proinflammatory cytokines (interleukin-8 and -6), and apoptotic proteins. All of these changes in indexes of biological effect were either diminished or inhibited by cell pretreatment with iron. Finally, percentage of neutrophils and total protein concentrations in an animal model instilled with silica were decreased by concurrent exposure to iron. We conclude that an initiating event in the response to particulate matter is a sequestration of cell and mitochondrial iron by endocytosed particle. The resultant oxidative stress and biological response after particle exposure are either diminished or inhibited by increasing the cell iron concentration.

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Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

November 15, 2013

Volume

305

Issue

10

Start / End Page

L712 / L724

Location

United States

Related Subject Headings

  • Silicon Dioxide
  • Reverse Transcriptase Polymerase Chain Reaction
  • Respiratory System
  • Real-Time Polymerase Chain Reaction
  • Reactive Oxygen Species
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Particulate Matter
  • Oxidative Stress
 

Citation

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ICMJE
MLA
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Ghio, A. J., Tong, H., Soukup, J. M., Dailey, L. A., Cheng, W.-Y., Samet, J. M., … Mutlu, G. M. (2013). Sequestration of mitochondrial iron by silica particle initiates a biological effect. Am J Physiol Lung Cell Mol Physiol, 305(10), L712–L724. https://doi.org/10.1152/ajplung.00099.2013
Ghio, Andrew J., Haiyan Tong, Joleen M. Soukup, Lisa A. Dailey, Wan-Yun Cheng, James M. Samet, Matthew J. Kesic, et al. “Sequestration of mitochondrial iron by silica particle initiates a biological effect.Am J Physiol Lung Cell Mol Physiol 305, no. 10 (November 15, 2013): L712–24. https://doi.org/10.1152/ajplung.00099.2013.
Ghio AJ, Tong H, Soukup JM, Dailey LA, Cheng W-Y, Samet JM, et al. Sequestration of mitochondrial iron by silica particle initiates a biological effect. Am J Physiol Lung Cell Mol Physiol. 2013 Nov 15;305(10):L712–24.
Ghio, Andrew J., et al. “Sequestration of mitochondrial iron by silica particle initiates a biological effect.Am J Physiol Lung Cell Mol Physiol, vol. 305, no. 10, Nov. 2013, pp. L712–24. Pubmed, doi:10.1152/ajplung.00099.2013.
Ghio AJ, Tong H, Soukup JM, Dailey LA, Cheng W-Y, Samet JM, Kesic MJ, Bromberg PA, Turi JL, Upadhyay D, Scott Budinger GR, Mutlu GM. Sequestration of mitochondrial iron by silica particle initiates a biological effect. Am J Physiol Lung Cell Mol Physiol. 2013 Nov 15;305(10):L712–L724.

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

EISSN

1522-1504

Publication Date

November 15, 2013

Volume

305

Issue

10

Start / End Page

L712 / L724

Location

United States

Related Subject Headings

  • Silicon Dioxide
  • Reverse Transcriptase Polymerase Chain Reaction
  • Respiratory System
  • Real-Time Polymerase Chain Reaction
  • Reactive Oxygen Species
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Particulate Matter
  • Oxidative Stress