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• W47729270 endingPage "902" @default.
• W47729270 startingPage "897" @default.
• W47729270 abstract "The acute-phase protein α1-antitrypsin (α1-AT) has been shown to inhibit the binding of transferrin to its cell-surface receptor. Here we demonstrate that in human erythroleukaemic cells (K562) α1-AT enhances the binding affinity of iron-regulatory protein (IRP), the central regulator of cellular iron metabolism, to iron-responsive elements. Activation of IRP by α1-AT is associated with a marked increase in transferrin receptor (trf-rec) mRNA levels in K562 and enhanced cell-surface expression of transferrin-binding sites, whereas ferritin production is decreased, although ferritin mRNA levels remain unchanged. In agreement with the well-established mechanism of cellular iron regulation, α1-AT seems to modulate trf-rec and ferritin expression primarily post-transcriptionally/translationally by influencing IRP activity. In contrast, α1-AT produces only minor changes in IRP activity, and subsequently in trf-rec expression and ferritin synthesis in THP-1 cells. Moreover the effects of α1-AT on iron homeostasis in K562 cannot be overcome by the addition of iron salts, whereas concomitant treatment of THP-1 with iron and α1-AT results in the same metabolic changes as the addition of iron alone. Because α1-AT blocks transferrin binding on K562 as well as on THP-1 cells, it is suggested, on the basis of the results presented here, (1) that erythroid and monocytic cells might differ in their dependence on transferrin-mediated iron supply and (2) that THP-1 might be able to acquire iron by a transferrin-independent iron uptake system. α1-AT might therefore be involved in the diversion of iron traffic between various cellular compartments under inflammatory conditions." @default.
• W47729270 created "2016-06-24" @default.
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• W47729270 date "1996-11-01" @default.
• W47729270 modified "2023-09-23" @default.
• W47729270 title "Divergent effects of α1-antitrypsin on the regulation of iron metabolism in human erythroleukaemic (K562) and myelomonocytic (THP-1) cells" @default.
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• W47729270 doi "https://doi.org/10.1042/bj3190897" @default.
• W47729270 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1217872" @default.
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