Iron Up-modulates the Expression of Transferrin Receptors during Monocyte-Macrophage Maturation

Testa, Ugo; Petrini, Marina; Quaranta, Maria Teresa; Pelosi, Elvira; Mastroberardino, G; Camagna, A; Boccoli, Giovanni; Sargiacomo, Massimo; Isacchi, G; Cozzi, Anna; Arosio, Paolo; Peschle, Cesare

doi:10.1016/s0021-9258(18)51612-4

Cited by 98 publications

(8 citation statements)

References 31 publications

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“…However, the overall conformation of the hTF 5'-UTR stem-loop predicted by computer modeling differs from the ferritin and transferrin receptor IRE's with a larger loop, lack of a bulging C, and different stem pairing. RNA-cytoplasmic protein binding assays have been used for studies of ferritin and TF receptor iron regulation (Aziz & Munro, 1986; Hentze etal., 1987a;Mullneretal., 1989;Barton Leibold et al, 1990;Testa et al, 1991). Similar binding assays were used here to demonstrate specific binding of liver cytoplasmic proteins to the human TF 5'-UTR and differential binding of extracts from iron treated versus control mice.…”

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confidence: 57%

Posttranscriptional regulation of chimeric human transferrin genes by iron

Cox¹,

Adrian²

1993

Biochemistry

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Transferrin, the transferrin receptor, and ferritin are integral to the body's management of iron, an element required for life but highly toxic when present in excess. The transferrin receptor and ferritin are regulated posttranscriptionally by iron: the transferrin receptor by mRNA stability and ferritin by mRNA translation. Results described here indicate that transferrin, like ferritin, is regulated by iron at the level of translation. Chimeric genes introduced into the mouse genome were composed of the human transferrin 5' regulatory region fused to the chloramphenicol acetyl transferase (CAT) reporter gene. Iron administration to transgenic mice resulted in a significant decrease of transferrin-directed CAT enzyme activity and CAT protein in liver, but no significant decrease in human transferrin-CAT mRNA levels. Binding of specific RNA iron regulatory elements by proteins in cytoplasmic extracts have been shown to regulate ferritin and transferrin receptor synthesis. Similar results have been obtained with transferrin mRNA. A decreased binding of human transferrin 5'-untranslated region RNA by factors in cytoplasmic extracts of livers from mice receiving iron was found when compared to extracts from control mice. A human transferrin RNA-protein complex migrated electrophoretically with the same mobility as a ferritin iron responsive element RNA-iron responsive element binding protein complex. The ferritin iron responsive element RNA also competed with the human transferrin 5'-untranslated region RNA-protein complexes formed and vice versa. Therefore, iron modulation of human transferrin may share a factor common or similar to that observed in ferritin and transferrin receptor iron modulation.

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confidence: 57%

Posttranscriptional regulation of chimeric human transferrin genes by iron

Cox¹,

Adrian²

1993

Biochemistry

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“…panied by high ferritin induction, suggesting that iron uptake and storage has a critical role in maturation of macrophages (17). Secondly, intraplaque hemorrhage, erythrophagocytosis, and apoptotic cell phagocytosis may result in accumulation of excessive cellular iron (5,18) and influence TfR1 expression (19). Thirdly, pro-inflammatory cytokines including IL-1, IL-2, c-IFN, and TNF-a modulate TfR1 regulation via different mechanisms (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Transferrin Receptor and Ferritin Related to Clinical Symptoms and Destabilization of Human Carotid Plaques

Xu²,

Forssell³

et al. 2008

Exp Biol Med (Maywood)

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Accumulation of tissue iron has been implicated in development of atherosclerotic lesions mainly because of increased iron-catalyzed oxidative injury. However, it remains unknown whether cellular iron import and storage in human atheroma are related to human atheroma development. We found that transferrin receptor 1 (TfR1), a major iron importer, is highly expressed in foamy macrophages and some smooth muscle cells in intimal lesions of human carotid atheroma, mainly in cytoplasmic accumulation patterns. In 52 human carotid atherosclerotic lesions, TfR1 expression was positively correlated with macrophage infiltration, ectopic lysosomal cathepsin L, and ferritin expression. Highly expressed TfR1 and ferritin in CD68-positive macrophages were significantly associated with development and severity of human carotid plaques, smoking, and patient's symptoms. The findings suggest that pathologic macrophage iron metabolism may contribute to vulnerability of human atheroma, established risk factors, and their clinical symptoms. The cytoplasmic overexpression of TfR1 may be the result of lysosomal dysfunction and ectopic accumulation of lysosomal cathepsin L caused by atheroma-relevant lipids in atherogenesis.

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“…Both T-cell proliferation and lymphokine release are iron dependent [4], transferrin receptor (TfR) expression by lymphocytes is stimulated by interleukin 2 (see [5]). In macrophages, iron upregulates TfRs [6].…”

Section: Introductionmentioning

confidence: 99%