RGD Reference Report - Deficiency in the divalent metal transporter 1 increases bleomycin-induced lung injury. - Rat Genome Database

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Deficiency in the divalent metal transporter 1 increases bleomycin-induced lung injury.

Authors: Yang, F  Stonehuerner, JG  Richards, JH  Nguyen, NB  Callaghan, KD  Haile, DJ  Ghio, AJ 
Citation: Yang F, etal., Biometals. 2010 Aug;23(4):657-67. Epub 2010 Mar 25.
RGD ID: 5688724
Pubmed: PMID:20336479   (View Abstract at PubMed)
DOI: DOI:10.1007/s10534-010-9326-0   (Journal Full-text)

Exposure to bleomycin can result in an inflammatory lung injury. The biological effect of this anti-neoplastic agent is dependent on its coordination of iron with subsequent oxidant generation. In lung cells, divalent metal transporter 1 (DMT1) can participate in metal transport resulting in control of an oxidative stress and tissue damage. We tested the postulate that metal import by DMT1 would participate in preventing lung injury after exposure to bleomycin. Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed to either bleomycin or saline via intratracheal instillation and the resultant lung injury was compared. Twenty-four h after instillation, the number of neutrophils and protein concentrations after bleomycin exposure were significantly elevated in the mk/mk mice relative to the wild-type mice. Similarly, levels of a pro-inflammatory mediator were significantly increased in the mk/mk mice relative to wild-type mice following bleomycin instillation. Relative to wild-type mice, mk/mk mice demonstrated lower non-heme iron concentrations in the lung, liver, spleen, and splenic, peritoneal, and liver macrophages. In contrast, levels of this metal were elevated in alveolar macrophages from mk/mk mice. We conclude that DMT1 participates in the inflammatory lung injury after bleomycin with mk/mk mice having increased inflammation and damage following exposure. This finding supports the hypothesis that DMT1 takes part in iron detoxification and homeostasis in the lung.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Lung Injury  ISOSlc11a2 (Mus musculus)5688724; 5688724 RGD 
Lung Injury  IMP 5688724 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc11a2  (solute carrier family 11 member 2)

Genes (Mus musculus)
Slc11a2  (solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2)

Genes (Homo sapiens)
SLC11A2  (solute carrier family 11 member 2)


Additional Information