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dc.contributor.authorZolea, Fabiana
dc.contributor.authorBiamonte, Flavia
dc.contributor.authorCandeloro, Patrizio
dc.contributor.authorDi Sanzo, Maddalena
dc.contributor.authorCozzi, Anna
dc.contributor.authorDi Vito, Anna
dc.contributor.authorQuaresima, Barbara
dc.contributor.authorLobello, Nadia
dc.contributor.authorTrecroci, Francesca
dc.contributor.authorDi Fabrizio, Enzo M.
dc.contributor.authorLevi, Sonia
dc.contributor.authorCuda, Giovanni
dc.contributor.authorCostanzo, Francesco
dc.date.accessioned2015-11-04T06:41:01Z
dc.date.available2015-11-04T06:41:01Z
dc.date.issued2015-10-17
dc.identifier.citationH ferritin silencing induces protein misfolding in K562 cells: A Raman analysis 2015 Free Radical Biology and Medicine
dc.identifier.issn08915849
dc.identifier.pmid26454082
dc.identifier.doi10.1016/j.freeradbiomed.2015.07.161
dc.identifier.urihttp://hdl.handle.net/10754/581665
dc.description.abstractThe redox state of the cell is involved in the regulation of many physiological functions as well as in the pathogenesis of several diseases, and is strictly dependent on the amount of iron in its catalytically active state. Alterations of iron homeostasis determine increased steady-state concentrations of Reactive Oxygen Species (ROS) that cause lipid peroxidation, DNA damage and altered protein folding. Ferritin keeps the intracellular iron in a non-toxic and readily available form and consequently plays a central role in iron and redox homeostasis. The protein is composed by 24 subunits of the H- and L-type, coded by two different genes, with structural and functional differences. The aim of this study was to shed light on the role of the single H ferritin subunit (FHC) in keeping the native correct protein three-dimensional structure. To this, we performed Raman spectroscopy on protein extracts from K562 cells subjected to FHC silencing. The results show a significant increase in the percentage of disordered structures content at a level comparable to that induced by H2O2 treatment in control cells. ROS inhibitor and iron chelator were able to revert protein misfolding. This integrated approach, involving Raman spectroscopy and targeted-gene silencing, indicates that an imbalance of the heavy-to-light chain ratio in the ferritin composition is able to induce severe but still reversible modifications in protein folding and uncovers new potential pathogenetic mechanisms associated to intracellular iron perturbation.
dc.language.isoen
dc.publisherElsevier BV
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0891584915005900
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Free Radical Biology and Medicine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Free Radical Biology and Medicine, 9 October 2015. DOI: 10.1016/j.freeradbiomed.2015.07.161
dc.subjectFerritin heavy chain
dc.subjectOxidative stress
dc.subjectProtein misfolding
dc.subjectRaman spectroscopy
dc.subjectK562
dc.titleH ferritin silencing induces protein misfolding in K562 cells: A Raman analysis
dc.typeArticle
dc.contributor.departmentMaterial Science and Engineering Program
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.identifier.journalFree Radical Biology and Medicine
dc.eprint.versionPost-print
dc.contributor.institutionDepartment of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta Campus, Catanzaro, Italy, 88100
dc.contributor.institutionBioNEM Laboratory, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta Campus, Catanzaro, Italy, 88100
dc.contributor.institutionSan Raffaele Scientific Institute, Division of Neuroscience, Milano, Italy, 20132
dc.contributor.institutionUniversity Vita-Salute San Raffaele, Milano, Italy, 20132
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personDi Fabrizio, Enzo M.
refterms.dateFOA2016-10-09T00:00:00Z
dc.date.published-online2015-10-17
dc.date.published-print2015-12


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