Iron release from ferritin induced by light and ionizing radiation

Wolszczak, Marian; Gajda, J

doi:10.1007/s11164-010-0155-0

Cited by 19 publications

(16 citation statements)

References 29 publications

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“…Several studies have shown that ionization radiations increased labile iron level [69,70]. Importantly, chelation of labile iron protect cells from ionizing radiation [71], indicating the critical role of increased labile iron in the therapeutic benefits.…”

Section: Iron Level As a Mechanistic Link Between Oncogenic States Anmentioning

confidence: 99%

Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism

et al. 2019

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Ferroptosis is a specialized iron-dependent cell death that is associated with lethal lipid peroxidation. Modulation of ferroptosis may have therapeutic potential since it has been implicated in various human diseases as well as potential antitumor activities. However, much remains unknown about the underlying mechanisms and genetic determinants of ferroptosis. Given the critical role of kinases in most biological processes and the availability of various kinase inhibitors, we sought to systemically identify kinases essential for ferroptosis. We performed a forward genetic-based kinome screen against ferroptosis in MDA-MB-231 cells triggered by cystine deprivation. This screen identified 34 essential kinases involved in TNFα and NF-kB signaling. Unexpectedly, the DNA damage response serine/threonine kinase ATM (mutated in Ataxia-Telangiectasia) was found to be essential for ferroptosis. The pharmacological or genetic inhibition of ATM consistently rescued multiple cancer cells from ferroptosis triggered by cystine deprivation or erastin. Instead of the canonical DNA damage pathways, ATM inhibition rescued ferroptosis by increasing the expression of iron regulators involved in iron storage (ferritin heavy and light chain, FTH1 and FTL) and export (ferroportin, FPN1). The coordinated changes of these iron regulators during ATM inhibition resulted in a lowering of labile iron and prevented the irondependent ferroptosis. Furthermore, we found that ATM inhibition enhanced the nuclear translocation of metal-regulatory transcription factor 1 (MTF1), responsible for regulating expression of Ferritin/FPN1 and ferroptosis protection. Genetic depletion of MTF-1 abolished the regulation of iron-regulatory elements by ATM and resensitized the cells to ferroptosis. Together, we have identified an unexpected ATM-MTF1-Ferritin/FPN1 regulatory axis as novel determinants of ferroptosis through regulating labile iron levels.

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Section: Iron Level As a Mechanistic Link Between Oncogenic States Anmentioning

confidence: 99%

Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism

et al. 2019

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“…Besides a chemical reducing agent, light or ionizing radiation is also used to trigger the mobilization of iron ions from ferritin (5). Small bidentate Fe(III) chelate ligands are capable of removing iron from the ferritin inorganic core via direct extraction followed by diffusion of the Fe(III)-chelate out of the protein shell (6), however, to achieve significant iron release, high ligand concentration (3.5-100 mM) is required due to the relatively low affinity of these ligands to iron.…”

Section: Introductionmentioning

confidence: 99%

The antitumor mechanism of di-2-pyridylketone 2-pyridine carboxylic acid hydrazone and its copper complex in ROS generation and topoisomerase inhibition, and hydrazone involvement in oxygen-catalytic iron mobilization

Huang

Sun

et al. 2015

International Journal of Oncology

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Iron depletion and stimulation of iron-dependent free radical damage is a rapidly developing field for chelation therapy, but the iron mobilization from ferritin by chelators has received less attention. In this study, the di-2-pyridylketone 2-pyridine carboxylic acid hydrazone (DPPCAH) and its copper complex was prepared and characterized by NMR and MS spectra. The proliferation inhibition assay showed that both DPPCAH and its copper complex exhibited selectively proliferation inhibition for HepG2 (IC50, 4.6 ± 0.2 µM for DPPACH and 1.3 ± 0.2 µM for its copper complex), but less inhibition for HCT-116 cell line (IC50, >100 µM for DPPACH and 7.8 ± 0.4 µM for its copper complex). The mechanistic studies revealed that DPPACH could remove iron from ferritin in a oxygen-catalytic manner, and contributed to redox activity of labile iron pool (LIP), that is less reported for the chelators that possess significant biological activity. The reactive oxygen species (ROS) generation and DNA cleavage assay in vitro and in vivo showed that both DPPACH-Fe(II) and DPPACH-Cu were redox-active species, indicating that ROS may mediate their antitumor activity. Further study revealed that both DPPACH and its copper complex displayed certain degree of inhibition of type II topoisomerase (Top) which contributed to their antitumor activity. Thus, the mechanism that iron mobilization by DPPACH from ferritin contributed to LIP was proposed, and both DPPACH and its copper complex were involved in ROS generation and Top II inhibition for their antitumor activities.

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“…The electrophoresis was terminated when two colored and differently charged thyroglobulin markers labelled with Cy-3.5 (Lumiprobe, Hunt Valley, MD, USA) reached nearly identical positions in the gel. For detection of ferritin absorbance, the gel was soaked with 0.5 M Bis-Tris-HCl, pH 7.0 at 37 • C. Ferritin has a broad absorption band in the ultraviolet region that tails into the visible region of the spectrum [103,104]. The absorbance under illumination at 365 nm was used to monitor ferritin in the native gel of sponge body tissue homogenates and photographed in a dark room.…”

Section: Protein Analyses 451 Native Gel Electrophoresismentioning

confidence: 99%

Conservative and Atypical Ferritins of Sponges

Adameyko

Burakov

Finoshin

et al. 2021

IJMS

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Ferritins comprise a conservative family of proteins found in all species and play an essential role in resistance to redox stress, immune response, and cell differentiation. Sponges (Porifera) are the oldest Metazoa that show unique plasticity and regenerative potential. Here, we characterize the ferritins of two cold-water sponges using proteomics, spectral microscopy, and bioinformatic analysis. The recently duplicated conservative HdF1a/b and atypical HdF2 genes were found in the Halisarca dujardini genome. Multiple related transcripts of HpF1 were identified in the Halichondria panicea transcriptome. Expression of HdF1a/b was much higher than that of HdF2 in all annual seasons and regulated differently during the sponge dissociation/reaggregation. The presence of the MRE and HRE motifs in the HdF1 and HdF2 promotor regions and the IRE motif in mRNAs of HdF1 and HpF indicates that sponge ferritins expression depends on the cellular iron and oxygen levels. The gel electrophoresis combined with specific staining and mass spectrometry confirmed the presence of ferric ions and ferritins in multi-subunit complexes. The 3D modeling predicts the iron-binding capacity of HdF1 and HpF1 at the ferroxidase center and the absence of iron-binding in atypical HdF2. Interestingly, atypical ferritins lacking iron-binding capacity were found in genomes of many invertebrate species. Their function deserves further research.

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Iron release from ferritin induced by light and ionizing radiation

Cited by 19 publications

References 29 publications

Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism

Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism

The antitumor mechanism of di-2-pyridylketone 2-pyridine carboxylic acid hydrazone and its copper complex in ROS generation and topoisomerase inhibition, and hydrazone involvement in oxygen-catalytic iron mobilization

Conservative and Atypical Ferritins of Sponges

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