Aluminum stimulates uptake of non-transferrin bound iron and transferrin bound iron in human glial cells.
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 on 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 1. These results suggest that aluminum disrupts iron homeostasis in the brain by several mechanisms including the transferrin receptor, a nontransferrin iron transporter, and ferritin.
Kim
Yongbae
Y
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, USA.
Olivi
Luisa
L
Cheong
Jae Hoon
JH
Maertens
Alex
A
Bressler
Joseph P
JP
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000328:Adult; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D001059:Apoproteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002712:Chlorides / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D008715:Methionine / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000378:metabolism; D013997:Time Factors; D014001:Tin / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism* / Q000493:pharmacokinetics; D014415:Tunicamycin / Q000494:pharmacology
D017607:Aluminum Compounds; D001059:Apoproteins; D002712:Chlorides; D002934:Cinnamates; D002951:Citrates; D005296:Ferrous Compounds; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D011990:Receptors, Transferrin; D014168:Transferrin; C028284:apotransferrin; C110714:holotransferrin; D014415:Tunicamycin; D000077410:Aluminum Chloride; C011401:ammoniacal ferrous citrate; D014001:Tin; D008715:Methionine; D007501:Iron; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid