Divalent metal transporter-1 decreases metal-related injury in the lung.
Exposure to airborne particulates makes the detoxification of metals a continuous challenge for the lungs. Based on the fate of iron in airway epithelial cells, we postulated that divalent metal transporter-1 (DMT1) participates in detoxification of metal associated with air pollution particles. Homozygous Belgrade rats, which are functionally deficient in DMT1, exhibited diminished metal transport from the lower respiratory tract and greater lung injury than control littermates when exposed to oil fly ash. Preexposure of normal rats to iron in vivo increased expression of the isoform of DMT1 protein that lacked an iron-response element (-IRE), accelerated metal transport out of the lung, and decreased injury after particle exposure. In contrast, normal rats preexposed to vanadium showed less expression of the -IRE isoform of DMT1, decreased metal transport, and greater pulmonary injury after particle instillation. Respiratory epithelial cells in culture gave similar results. Also, DMT1 mRNA and protein expression for the -IRE isoform increased or decreased in these cells when exposed to iron or vanadium, respectively. These results thus demonstrate for the first time a primary role for DMT1 in lung metal transport and detoxification.
Ghio
Andrew J
AJ
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Ghio.Andy@epa.gov
Piantadosi
Claude A
CA
Wang
Xinchao
X
Dailey
Lisa A
LA
Stonehuerner
Jacqueline D
JD
Madden
Michael C
MC
Yang
Funmei
F
Dolan
Kevin G
KG
Garrick
Michael D
MD
Garrick
Laura M
LM
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D005290:Ferric Compounds / Q000494:pharmacology; D007150:Immunohistochemistry; D007501:Iron / Q000493:pharmacokinetics; D033862:Iron-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D008171:Lung Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008670:Metals / Q000378:metabolism; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014639:Vanadium / Q000493:pharmacokinetics; D017968:Vanadium Compounds / Q000494:pharmacology; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D005290:Ferric Compounds; D007501:Iron; D033862:Iron-Binding Proteins; D008670:Metals; D020033:Protein Isoforms; D000644:Quaternary Ammonium Compounds; D014639:Vanadium; D017968:Vanadium Compounds; D000099236:Solute Carrier Family 11, Member 2; C034028:vanadyl sulfate; C013531:ferric ammonium citrate