H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

Zolea, Fabiana; Biamonte, Flavia; Candeloro, Patrizio; Sanzo, Maddalena Di; Cozzi, Anna; Vito, Anna Di; Quaresima, Barbara; Lobello, Nadia; Trecroci, Francesca; Fabrizio, E. Di; Levi, Sonia; Cuda, Giovanni; Costanzo, Francesco

doi:10.1016/j.freeradbiomed.2015.07.161

Cited by 25 publications

(23 citation statements)

References 43 publications

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“…A number of studies have shown that the heavy chain of ferritin is a multifunctional protein implicated in several cellular pathways, including differentiation [ 40 ], neoplastic transformation [ 41 ], chemokine signalling [ 18 ], control of proper protein folding [ 42 ] and cell proliferation [ 20 , 21 ]. On the other hand, the FHC main role is still represented by its capacity to buffer intracellular free iron through its ferroxidase activity.…”

Section: Discussionmentioning

confidence: 99%

Caffeine Positively Modulates Ferritin Heavy Chain Expression in H460 Cells: Effects on Cell Proliferation

et al. 2016

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Both the methylxanthine caffeine and the heavy subunit of ferritin molecule (FHC) are able to control the proliferation rate of several cancer cell lines. While caffeine acts exclusively as a negative modulator of cell proliferation, FHC might reduce or enhance cell viability depending upon the different cell type. In this work we have demonstrated that physiological concentrations of caffeine reduce the proliferation rate of H460 cells: along with the modulation of p53, pAKT and Cyclin D1, caffeine also determines a significant FHC up-regulation through the activation of its transcriptional efficiency. FHC plays a central role in the molecular pathways modulated by caffeine, ending in a reduced cell growth, since its specific silencing by siRNA almost completely abolishes caffeine effects on H460 cell proliferation. These results allow the inclusion of ferritin heavy subunits among the multiple molecular targets of caffeine and open the way for studying the relationship between caffeine and intracellular iron metabolism.

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Section: Discussionmentioning

confidence: 99%

Caffeine Positively Modulates Ferritin Heavy Chain Expression in H460 Cells: Effects on Cell Proliferation

et al. 2016

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“…However, Raman microimaging offers the possibility to better understand the biochemical mechanisms with relatively small expenditures in terms of time and labor. It is worth mentioning that Raman microspectroscopy has attracted a large interest from the biochemistry/biomedical community in the last decade and several works have been proposed regarding lipidomics, 14,15 proteomics, 16,17 stem cells differentiation, 18 cancer stem cell biochemistry, 19 investigation of exosomes derived from tumor cells, 20 comparative studies of embryonic stem cells, and induced pluripotent stem cells. 21,22 In addition, in the field of brain tissue analysis, several works have been using Raman spectroscopy with different purposes, such as the determination of brain edema in tumor diseases, 23 imaging of brain injury where Raman signatures are correlated to apoptosis by evidencing a Caspase over-expression through immunohistochemistry, 24 label-free tissue imaging, 25 investigation of the neuroprotective role of ascorbic acid against brain injury due to oxidative stress, 26 and, very recently, Raman spectroscopy in combination with PCA analysis has been used to discriminate between normal, ischemic, and nNOS inhibitor-treated brain tissues after ischemic events.…”

Section: Introductionmentioning

confidence: 99%

Key Role of Cytochrome C for Apoptosis Detection Using Raman Microimaging in an Animal Model of Brain Ischemia with Insulin Treatment

et al. 2019

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Brain ischemia represents a leading cause of death and disability in industrialized countries. To date, therapeutic intervention is largely unsatisfactory and novel strategies are required for getting better protection of neurons injured by cerebral blood flow restriction. Recent evidence suggests that brain insulin leads to protection of neuronal population undergoing apoptotic cell death via modulation of oxidative stress and mitochondrial cytochrome c (CytC), an effect to be better clarified. In this work, we investigate on the effect of insulin given intracerebroventricular (ICV) before inducing a transient global ischemia by bilateral occlusion of the common carotid arteries (BCCO) in Mongolian gerbils (MG). The transient (3 min) global ischemia in MG is observed to produce neurodegenerative effect mainly into CA3 hippocampal region, 72 h after cerebral blood restriction. Intracerebroventricular microinfusion of insulin significantly prevents the apoptosis of CA3 hippocampal neurons. Histological observation, after hematoxylin and eosin staining, puts in evidence the neuroprotective role of insulin, but Raman microimaging provides a clearer insight in the CytC mechanism underlying the apoptotic process. Above all, CytC has been revealed to be an outstanding, innate Raman marker for monitoring the cells status, thanks to its resonant scattering at 530 nm of incident wavelength and to its crucial role in the early stages of cells apoptosis. These data support the hypothesis of an insulin-dependent neuroprotection and antiapoptotic mechanism occurring in the brain of MG undergoing transient brain ischemia. The observed effects occurred without any peripheral change on serum glucose levels, suggesting an alternative mechanism of insulin-induced neuroprotection.

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“…Besides iron metabolism, FHC controls additional biochemical pathways such as cell proliferation [ 13 ], p53 regulation [ 14 ], chemokine signalling [ 15 ], angiogenesis [ 16 ], regulation of oncomiRNAs network [ 17 ], control of proper protein folding [ 18 ], stem cell expansion [ 19 ]. In some pathways FHC physically interacts with target molecules independently from its ferroxidase activity [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Epithelial-to-mesenchymal transition in FHC-silenced cells: the role of CXCR4/CXCL12 axis

Aversa

Zolea

Ieranò³

et al. 2017

J Exp Clin Cancer Res

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BackgroundFerritin plays a central role in the intracellular iron metabolism; the molecule is a nanocage of 24 subunits of the heavy and light types. The heavy subunit (FHC) is provided of a ferroxidase activity and thus performs the key transformation of iron in a non-toxic form. Recently, it has been shown that FHC is also involved in additional not iron-related critical pathways including, among the others, p53 regulation, modulation of oncomiRNAs expression and chemokine signalling. Epithelial to mesenchymal transition (EMT) is a cellular mechanism by which the cell acquires a fibroblast-like phenotype along with a decreased adhesion and augmented motility. In this work we have focused our attention on the role of the FHC on EMT induction in the human cell lines MCF-7 and H460 to elucidate the underlying molecular mechanisms.MethodsTargeted silencing of the FHC was performed by lentiviral-driven shRNA strategy. Reconstitution of the FHC gene product was obtained by full length FHC cDNA transfection with Lipofectamine 2000. MTT and cell count assays were used to evaluate cell viability and proliferation; cell migration capability was assayed by the wound-healing assay and transwell strategy. Quantification of the CXCR4 surface expression was performed by flow cytometry.ResultsExperimental data indicated that FHC-silenced MCF-7 and H460 cells (MCF-7shFHC, H460shFHC) acquire a mesenchymal phenotype, accompanied by a significant enhancement of their migratory and proliferative capacity. This shift is coupled to an increase in ROS production and by an activation of the CXCR4/CXCL12 signalling pathway. We present experimental data indicating that the cytosolic increase in ROS levels is responsible for the enhanced proliferation of FHC-silenced cells, while the higher migration rate is attributable to a dysregulation of the CXCR4/CXCL12 axis.ConclusionsOur findings indicate that induction of EMT, increased migration and survival depend, in MCF-7 and H460 cells, on the release of FHC control on two pathways, namely the iron/ROS metabolism and CXCR4/CXCL12 axis. Besides constituting a further confirmation of the multifunctional nature of FHC, this data also suggest that the analysis of FHC amount/function might be an important additional tool to predict tumor aggressiveness.

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H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

Cited by 25 publications

References 43 publications

Caffeine Positively Modulates Ferritin Heavy Chain Expression in H460 Cells: Effects on Cell Proliferation

Caffeine Positively Modulates Ferritin Heavy Chain Expression in H460 Cells: Effects on Cell Proliferation

Key Role of Cytochrome C for Apoptosis Detection Using Raman Microimaging in an Animal Model of Brain Ischemia with Insulin Treatment

Epithelial-to-mesenchymal transition in FHC-silenced cells: the role of CXCR4/CXCL12 axis

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