Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 220, Issue 3, Pages 349-356Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2007.02.001
Keywords
aluminum; iron; glial transporters; transferrin
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Funding
- NIEHS NIH HHS [P30 ES003819-19, P30 ES003819] Funding Source: Medline
- PHS HHS [03819] Funding Source: Medline
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Aluminum and other trivalent metals were shown to stimulate uptake of transferrin bound iron and nontransferrin bound iron in erytholeukemia and hepatoma cells. Because of the association between aluminum and Alzheimer's Disease, and findings of higher levels of iron in Alzheimer's disease brains, the effects of aluminum oil iron homeostasis were examined in a human glial cell line. Aluminum stimulated dose- and time-dependent uptake of nontransferrin bound iron and iron bound to transferrin. A transporter was likely involved in the uptake of nontransferrin iron because uptake reached saturation, was temperature-dependent, and attenuated by inhibitors of protein synthesis. Interestingly, the effects of aluminum were not blocked by inhibitors of RNA synthesis. Aluminum also decreased the amount of iron bound to ferritin though it did not affect levels of divalent metal transporter I. These results suggest that aluminum disrupts iron homeostasis in the brain by several mechanisms including the transferrin receptor, a nontransferrin iron transporter, and ferritin. (c) 2007 Elsevier Inc. All rights reserved.
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