Transferrin enhances the antiproliferative effect of aluminum on osteoblast-like cells.
Aluminum (Al) retention in the body can cause metabolic bone disease. This disorder is characterized by reductions in the number of osteoblasts, a feature that suggests a disturbance in bone cell proliferation or differentiation. Because Al as well as iron (Fe) can bind to transferrin (TF) in plasma, the role of TF as a modifier of osteoblast proliferation was examined in UMR-106-01 osteoblast-like cells by measuring the incorporation of tritiated thymidine ([3H]-TdR) into DNA (counts.min-1.microgram cell protein-1, means +/- SE) during 48-h incubations in serum-free medium (SFM). In the absence of TF, DNA synthesis decreased when media levels of Al exceeded 6-10 microM. The mitogenic response to physiological levels of unsaturated TF (apo-TF) was attenuated however during incubations with TF that was partially saturated with Al (Al-TF). A similar inhibitory response was seen in cells incubated with the antiproliferative agent gallium (Ga) when added to SFM as partially saturated Ga-TF. TF produced a shift to the left in the inhibitory dose-response curve to Al in osteoblast-like cells; thus, DNA synthesis decreased at substantially lower media concentrations of Al in cells grown in SFM containing partially saturated Al-TF. The results indicate that TF is an important determinant of the inhibitory effect of Al on DNA synthesis by osteoblast-like cells at the micromolar levels of Al that can occur in plasma in vivo.
Kasai
K
K
Medical Service, Sepulveda Veterans Administration Medical Center 91343.
Hori
M T
MT
Goodman
W G
WG
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D001059:Apoproteins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D004261:DNA Replication / Q000187:drug effects*; D004357:Drug Synergism; D005708:Gallium / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D012516:Osteosarcoma; D051381:Rats; D012513:Sarcoma, Experimental; D013936:Thymidine / Q000378:metabolism; D014168:Transferrin / Q000494:pharmacology*; D014316:Tritium
D001059:Apoproteins; D002951:Citrates; D014168:Transferrin; C028284:apotransferrin; D014316:Tritium; D019343:Citric Acid; D005708:Gallium; D000535:Aluminum; D007501:Iron; D013936:Thymidine