title: Murine macrophages response to iron.
abstract: Macrophages play a critical role at the crossroad between iron metabolism and immunity, being able to store and recycle iron derived from the phagocytosis of senescent erythrocytes. The way by which macrophages manage non-heme iron at physiological concentration is still not fully understood. We investigated protein changes in mouse bone marrow macrophages incubated with ferric ammonium citrate (FAC 10 μM iron). Differentially expressed spots were identified by nano RP-HPLC-ESI-MS/MS. Transcriptomic, metabolomics and western immunoblotting analyses complemented the proteomic approach. Pattern analysis was also used for identifying networks of proteins involved in iron homeostasis. FAC treatment resulted in higher abundance of several proteins including ferritins, cytoskeleton related proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) at the membrane level, vimentin, arginase, galectin-3 and macrophage migration inhibitory factor (MIF). Interestingly, GAPDH has been recently proposed to act as an alternative transferrin receptor for iron acquisition through internalization of the GAPDH-transferrin complex into the early endosomes. FAC treatment also induced the up-regulation of oxidative stress-related proteins (PRDX), which was further confirmed at the metabolic level (increase in GSSG, 8-isoprostane and pentose phosphate pathway intermediates) through mass spectrometry-based targeted metabolomics approaches. This study represents an example of the potential usefulness of "integarated omics" in the field of iron biology, especially for the elucidation of the molecular mechanisms controlling iron homeostasis in normal and disease conditions. This article is part of a Special Issue entitled: Integrated omics.
authors: University of Verona, Department of Biotechnology, Strada Le Grazie 15, 37134 Verona, Italy. polati.rita@gmail.com
authors: Rita
authors: R
authors: Polati
authors: Annalisa
authors: A
authors: Castagna
authors: Alessandra Maria
authors: AM
authors: Bossi
authors: Tiziana
authors: T
authors: Alberio
authors: Ivana
authors: I
authors: De Domenico
authors: Jerry
authors: J
authors: Kaplan
authors: Anna Maria
authors: AM
authors: Timperio
authors: Lello
authors: L
authors: Zolla
authors: Federica
authors: F
authors: Gevi
authors: Angelo
authors: A
authors: D'Alessandro
authors: Ryan
authors: R
authors: Brunch
authors: Oliviero
authors: O
authors: Olivieri
authors: Domenico
authors: D
authors: Girelli
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D005290:Ferric Compounds / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007501:Iron / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D055442:Metabolome / Q000187:drug effects / Q000502:physiology*; D055432:Metabolomics / Q000379:methods; D051379:Mice; D020543:Proteome / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology
chemical_list: D005290:Ferric Compounds; D020543:Proteome; D000644:Quaternary Ammonium Compounds; D007501:Iron; C013531:ferric ammonium citrate