Multi-vitamin products, nutritional supplements and parents tout the need for such mineral elements as calcium, zinc, phosphorus, iron and others.
Iron, for example, is a nutritional prerequisite to power life itself. When blood doesn't get enough iron from the gut, we become anemic. One of the body's coping mechanisms is to produce more of a protein called divalent metal transporter 1 (DMT1) in the gastrointestinal lining cells to bring into the body as much iron as possible. Until recently DMT1 was exclusively studied for its nutritional role in transporting iron.
But put iron or other air-borne particulates into our lungs and they can cause health problems ranging from asthma and acute respiratory distress syndrome to asbestosis and lung cancer.
In a recently-published paper a group of EPA-led lung researchers reported experiments demonstrating for the first time that "DMT1 is essential for the transport and detoxification of some metals associated with an air pollution particle that damages the pulmonary epithelial surface."
The paper "Divalent metal transporter-1 decreases metal-related injury in the lung" appears in the American Journal of Physiology-Lung Cellular and Molecular Physiology, published by the American Physiological Society. Research was performed by Andrew J. Ghio, Lisa A. Dailey, Jacqueline D. Stonehuerner and Michael C. Madden from the U.S. Environmental Protection Agency; Claude A. Piantadosi of Duke University; Xinchao Wang of University of North Carolina; Funmei Yang of University of Texas; and Kevin G. Dolan, Michael D. Garrick and Laura M. Garrick of SUNY-Buffalo.
Lead researcher Andrew Ghio said this breakthrough discovery of DMT1 lung protection could prompt studies of its roles in other organs where it's found. "For instance, DMT1 is in the liver, kidneys and brain, where it's not needed for nutritional purposes," Ghio said, "and since iron is implicated in everything from infections to cancers, it's not unreasonable to believe DMT1 could serve as a therapeutic target in those, as well as even Alzheimer's."
Using an "oil fly ash" high in iron and vanadium collected from a Florida power plant burning low sulfur oil as the insult, the researchers tested exposure to normal rats as well as "Belgrade" rats, which are functionally deficient in DMT1 because of a mutation. They also performed parallel tests in vitro, as well as testing how "pre-conditioning" with various foreign metallic insults might affect gene expression and resulting lung damage.
One key to how DMT1 works is by generating two alternatively spliced messenger RNAs that differ by the presence (+) or absence (-) of an Iron-Response Element (thus –IRE or +IRE). In contrast to the gastrointestinal tract where the +IRE form dominates, there is more -IRE DMT1 in the lung. The paper noted that in the lung, "there is an IRE-independent iron-regulatory pathway for control of DMT1 expression of the –IRE isoform of DMT1, whereas the +IRE isoform shows little response to the metal."
The authors said that before their results, it could have been argued that "the chain of events described here (iron exposure increasing –IRE DMT1 expression leading to metal uptake with sequestration of iron)…is just a set of associations." However, the Belgrade data "rule out these alternatives and support the argument that this chain of events is a set of causal relationships because (these rats) have defective DMT1," which diminishes transport activity. "This transport deficiency in the Belgrade rat renders this animal ineffective at controlling the oxidative stress presented by the (ash) particle, so that greater tissue injury results.