Iron accumulation and expression of iron-related proteins following murine exposure to crocidolite.
We tested the postulate that asbestos exposure alters iron homeostasis in the mouse lung. Crocidolite asbestos (100 microg intratracheally) was instilled into C57BL/6 mice. TiO2 served as a control exposure. Using iron staining and immunohistochemistry, concentrations of this metal and expression of several iron transport and storage proteins were evaluated at one day and one month following asbestos exposure. Iron was not stainable one day following asbestos instillation but was increased one month later. There was an elevated expression of duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), and ferritin at both one day and one month after crocidolite exposure. While ferroportin (FPN1) expression was increased one day after asbestos exposure, levels of this metal exporter had returned to baseline at one month. TiO2 did not affect changes in either the iron concentration or the expression of these iron-related proteins at one day and one month. We conclude that asbestos exposure alters lung iron homeostasis with an accumulation of the metal resulting. Elevations in available iron affect changes in the expression of Dcytb, DMT1, ferritin, and FPN1, which further modify metal homeostasis in the lung.
Ghio
Andrew
A
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC 27711, USA. ghio.andy@epa.gov
Tan
Roderick J
RJ
Ghio
Kathleen
K
Fattman
Cheryl L
CL
Oury
Tim D
TD
D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D027682:Cation Transport Proteins / Q000378:metabolism*; D045303:Cytochromes b / Q000378:metabolism*; D004386:Duodenum / Q000201:enzymology; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D017638:Asbestos, Crocidolite; D027682:Cation Transport Proteins; D045303:Cytochromes b; D007501:Iron; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2