H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis
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ArticleAuthors
Zolea, FabianaBiamonte, Flavia
Candeloro, Patrizio

Di Sanzo, Maddalena
Cozzi, Anna
Di Vito, Anna
Quaresima, Barbara
Lobello, Nadia
Trecroci, Francesca
Di Fabrizio, Enzo M.

Levi, Sonia
Cuda, Giovanni

Costanzo, Francesco
KAUST Department
Material Science and Engineering ProgramPhysical Science and Engineering (PSE) Division
Date
2015-10-17Online Publication Date
2015-10-17Print Publication Date
2015-12Permanent link to this record
http://hdl.handle.net/10754/581665
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The 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.Citation
H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis 2015 Free Radical Biology and MedicinePublisher
Elsevier BVPubMed ID
26454082Additional Links
http://linkinghub.elsevier.com/retrieve/pii/S0891584915005900ae974a485f413a2113503eed53cd6c53
10.1016/j.freeradbiomed.2015.07.161
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