H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis
Di Sanzo, Maddalena
Di Vito, Anna
Di Fabrizio, Enzo M.
KAUST DepartmentMaterial Science and Engineering Program
Physical Science and Engineering (PSE) Division
Online Publication Date2015-10-17
Print Publication Date2015-12
Permanent link to this recordhttp://hdl.handle.net/10754/581665
MetadataShow full item record
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.
CitationH ferritin silencing induces protein misfolding in K562 cells: A Raman analysis 2015 Free Radical Biology and Medicine
- Ferritin heavy chain-mediated iron homeostasis and subsequent increased reactive oxygen species production are essential for epithelial-mesenchymal transition.
- Authors: Zhang KH, Tian HY, Gao X, Lei WW, Hu Y, Wang DM, Pan XC, Yu ML, Xu GJ, Zhao FK, Song JG
- Issue date: 2009 Jul 1
- Identification of H ferritin-dependent and independent genes in K562 differentiating cells by targeted gene silencing and expression profiling.
- Authors: Misaggi R, Di Sanzo M, Cosentino C, Bond HM, Scumaci D, Romeo F, Stellato C, Giurato G, Weisz A, Quaresima B, Barni T, Amato F, Viglietto G, Morrone G, Cuda G, Faniello MC, Costanzo F
- Issue date: 2014 Feb 10
- Regulation of LIP level and ROS formation through interaction of H-ferritin with G-CSF receptor.
- Authors: Yuan X, Cong Y, Hao J, Shan Y, Zhao Z, Wang S, Chen J
- Issue date: 2004 May 21
- Sequence analysis of dolphin ferritin H and L subunits and possible iron-dependent translational control of dolphin ferritin gene.
- Authors: Takaesu A, Watanabe K, Takai S, Sasaki Y, Orino K
- Issue date: 2008 Oct 27
- Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes.
- Authors: Omiya S, Hikoso S, Imanishi Y, Saito A, Yamaguchi O, Takeda T, Mizote I, Oka T, Taneike M, Nakano Y, Matsumura Y, Nishida K, Sawa Y, Hori M, Otsu K
- Issue date: 2009 Jan