Altered Ferritin Subunit Composition: Change in Iron Metabolism in Lens Epithelial Cells and Downstream Effects on Glutathione Levels and VEGF Secretion

Harned, J.; Ferrell, J.; Lall, Marilyn M.; Fleisher, Lloyd N.; Nagar, Steven; Goralska, M.; McGahan, M.C.

doi:10.1167/iovs.09-3861

Cited by 16 publications

(12 citation statements)

References 29 publications

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“…Interestingly, downregulation of the H-chain of FT resulted in a marked compensatory increase in FTL levels, but much less so the other way around, indicating the existence of a regulatory feedback mechanism, which has also been implicated before by other groups (Kakhlon et al 2001;Harned et al 2010). When combined attenuation of both FT chains was conducted, FTL was only slightly depressed, probably because of contradictory mechanisms with FTL-siRNA trying to deplete it while, simultaneously, the low FTH level initiates FTL transcription.…”

Section: Discussionmentioning

confidence: 70%

Attenuation of iron‐binding proteins in ARPE‐19 cells reduces their resistance to oxidative stress

Karlsson

Kurz

2016

Acta Ophthalmologica

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Section: Discussionmentioning

confidence: 70%

Attenuation of iron‐binding proteins in ARPE‐19 cells reduces their resistance to oxidative stress

Karlsson

Kurz

2016

Acta Ophthalmologica

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“…Recently, self-assembly of ferritin was shown to be required for achieving ferroxidase catalytic activity [ 46 ]. Given that ferritins isolated from different mammalian tissues show differences in the ratios of the two types of their subunits, the regulation of ferritin assembly in vivo requires further investigation [ 47 , 48 , 49 , 50 , 51 , 52 , 53 ].…”

Section: Introductionmentioning

confidence: 99%

Ferritin Assembly in Enterocytes of Drosophila melanogaster

Rosas‐Arellano

Vásquez-Procopio

Gambis

et al. 2016

IJMS

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Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH) and Ferritin 2 Light Chain Homolog (Fer2LCH) are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated.

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“…These results were also confirmed in vivo and proposed as molecular basis of the high recurrence of breast cancer in young patients [48,49]. Conversely, a study by Harned, et al highlights that the H-ferritin silencing and the consequent alteration in ferritin H:L ratio causes decreased nuclear translocation of HIF1-alpha and VEGF secretion [50].…”

Section: Ferritin and Angiogenesismentioning

confidence: 74%

Ferritin Heavy Chain: From Redox Cycling to Cancer Biology

Biamonte¹

2018

IJBP

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Iron is an essential nutrient for physiological cellular functions: as cofactor for key enzymes, it is involved in DNA duplication and repair thus representing a key element for cell replication, metabolism and growth. Due to its main role in iron storage, ferritin has been largely referred as redox-related protein for many years. However, increasing evidences suggest that perturbations of intracellular steady state amount of ferritin, and particularly of its heavy subunit (FHC), are key events in the pathogenesis of cancer initiation and progression. In the past decade many studies have demonstrated that FHC participates in cancer related pathways such as growth suppressor evasion, angiogenesis, epithelial to mesenchymal transition (EMT), dysregulation of chemokine signalling and enhanced stem cell expansion. The molecular mechanisms whereby FHC exerts these activities are either iron-dependent or ironindependent. Among the latters, the ability to regulate critical oncogenes (c-myc, NF-kB) or tumor suppressors (p53) as well as to modulate oncomiRNAs expression and chemokine signalling (CXCR4) strongly suggests that FHC is a much more versatile protein than simply iron storage. The deep understanding of these novel and still not completely characterized functions, as well as the discovery of other potential properties, position ferritin as a promising target in cancer therapy.

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Altered Ferritin Subunit Composition: Change in Iron Metabolism in Lens Epithelial Cells and Downstream Effects on Glutathione Levels and VEGF Secretion

Cited by 16 publications

References 29 publications

Attenuation of iron‐binding proteins in ARPE‐19 cells reduces their resistance to oxidative stress

Attenuation of iron‐binding proteins in ARPE‐19 cells reduces their resistance to oxidative stress

Ferritin Assembly in Enterocytes of Drosophila melanogaster

Ferritin Heavy Chain: From Redox Cycling to Cancer Biology

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