Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ferritin expression modulates cell cycle dynamics and cell responsiveness to H-ras-induced growth via expansion of the labile iron pool.

ABSTRACT: Repression or overexpression of ferritin accelerated or retarded cell cycling respectively, via changes in the cellular labile iron pool (LIP). A rise in LIP is caused by ferritin repression enhanced growth, induced by H-ras, and reverted growth arrest is induced by dominant negative H-ras. The studies indicate that repression of ferritin expression provides a mechanism by which certain oncogenes lead to cell growth stimulation.

SUBMITTER: Kakhlon O

PROVIDER: S-EPMC1222495 | biostudies-other | 2002 May

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Repression of the heavy ferritin chain increases the labile iron pool of human K562 cells.

Project description:The role of ferritin in the modulation of the labile iron pool was examined by repressing the heavy subunit of ferritin in K562 cells transfected with an antisense construct. Repression of the heavy ferritin subunit evoked an increase in the chemical levels and pro-oxidant activity of the labile iron pool and, in turn, caused a reduced expression of transferrin receptors and increased expression of the light ferritin subunit.

| S-EPMC1221840 | biostudies-other

The Labile Iron Pool Reacts Rapidly and Catalytically with Peroxynitrite.

Project description:While investigating peroxynitrite-dependent oxidation in murine RAW 264.7 macrophage cells, we observed that removal of the Labile Iron Pool (LIP) by chelation increases the intracellular oxidation of the fluorescent indicator H2DCF, so we concluded that the LIP reacts with peroxynitrite and decreases the yield of peroxynitrite-derived oxidants. This was a paradigm-shifting finding in LIP biochemistry and raised many questions. In this follow-up study, we address fundamental properties of the interaction between the LIP and peroxynitrite by using the same cellular model and fluorescence methodology. We have identified that the reaction between the LIP and peroxynitrite has catalytic characteristics, and we have estimated that the rate constant of the reaction is in the range of 106 to 107 M-1s-1. Together, these observations suggest that the LIP represents a constitutive peroxynitrite reductase system in RAW 264.7 cells.

| S-EPMC8466499 | biostudies-literature

Cancer cell death induced by ferritins and the peculiar role of their labile iron pool.

Project description:Cellular uptake of human H-ferritin loaded with 50 or 350 iron ions results in significant cytotoxicity on HeLa cells at submicromolar concentrations. Conversely, Horse Spleen Ferritin, that can be considered a model of L-cages, as it contains only about 10% of H subunits, even when loaded with 1000 iron ions, is toxic only at >1 order of magnitude higher protein concentrations. We propose here that the different cytotoxicity of the two ferritin cages originates from the presence in H-ferritin of a pool of non-biomineralized iron ions bound at the ferroxidase catalytic sites of H-ferritin subunits. This iron pool is readily released during the endosomal-mediated H-ferritin internalization.

| S-EPMC6021343 | biostudies-literature

Iron-independent phosphorylation of iron regulatory protein 2 regulates ferritin during the cell cycle.

Project description:Iron regulatory protein 2 (IRP2) is a key iron sensor that post-transcriptionally regulates mammalian iron homeostasis by binding to iron-responsive elements (IREs) in mRNAs that encode proteins involved in iron metabolism (e.g. ferritin and transferrin receptor 1). During iron deficiency, IRP2 binds IREs to regulate mRNA translation or stability, whereas during iron sufficiency IRP2 is degraded by the proteasome. Here, we identify an iron-independent IRP2 phosphorylation site that is regulated by the cell cycle. IRP2 Ser-157 is phosphorylated by Cdk1/cyclin B1 during G(2)/M and is dephosphorylated during mitotic exit by the phosphatase Cdc14A. Ser-157 phosphorylation during G(2)/M reduces IRP2 RNA-binding activity and increases ferritin synthesis, whereas Ser-157 dephosphorylation during mitotic exit restores IRP2 RNA-binding activity and represses ferritin synthesis. These data show that reversible phosphorylation of IRP2 during G(2)/M has a role in modulating the iron-independent expression of ferritin and other IRE-containing mRNAs during the cell cycle.

| S-EPMC2527096 | biostudies-literature

A reactivity-based probe of the intracellular labile ferrous iron pool.

Project description:Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the aminonucleoside puromycin. Puromycin leaves a permanent and dose-dependent mark on treated cells that can be detected with high sensitivity and precision using a high-content, plate-based immunofluorescence assay. Using this new probe and screening approach, we detected alteration of cellular labile Fe(II) in response extracellular iron conditioning, overexpression of iron storage and/or export proteins, and post-translational regulation of iron export. We also used this new tool to demonstrate that labile Fe(II) pools are larger in cancer cells than in nontumorigenic cells.

| S-EPMC4990480 | biostudies-literature

Management versus miscues in the cytosolic labile iron pool: The varied functions of iron chaperones.

Project description:Iron-containing proteins rely on the incorporation of a set of iron cofactors for activity. The cofactors must be synthesized or assembled from raw materials located within the cell. The chemical nature of this pool of raw material - referred to as the labile iron pool - has become clearer with the identification of micro- and macro-molecules that coordinate iron within the cell. These molecules function as a buffer system for the management of intracellular iron and are the focus of this review, with emphasis on the major iron chaperone protein coordinating the labile iron pool: poly C-binding protein 1.

| S-EPMC7484093 | biostudies-literature

Artesunate induces ER-derived-ROS-mediated cell death by disrupting labile iron pool and iron redistribution in hepatocellular carcinoma cells.

Project description:Aberrant iron homeostasis is a typical characteristic of Hepatocellular carcinoma (HCC), and perturbation of iron metabolism is an effective strategy for HCC therapy. However, there are few safe and effective targeting agents available in clinical practices. The artemisinin and its derivatives have shown potential anti-cancer activity by disturbing cellular iron homeostasis, but the specific mechanism is still unclear. In this study, we demonstrate that Artesunate (ART), a water-soluble anti-malaria agent in clinical use, can regulate the labile iron pool (LIP) and effectively induce ROS-dependent cell death in multiple HCC cells. Mechanistically, ART increases the LIP by promoting lysosomal degradation of iron-storage protein ferritin through acidizing lysosomes. Then the accumulation of labile iron in the endoplasmic reticulum (ER) promotes excessive reactive oxygen species (ROS) production and severe ER disruption, which leads to cell death. Our results provide a new understanding of how ART modulates iron metabolism in HCC cells at the subcellular level, demonstrate the significance of endoplasmic reticulum as iron-vulnerability of HCC cells. More importantly, our findings suggest ART is a safe and potential anti-HCC agent via disturbing iron homeostasis.

| S-EPMC7994160 | biostudies-literature

Parasite maturation and host serum iron influence the labile iron pool of erythrocyte stage Plasmodium falciparum.

Project description:Iron is a critical and tightly regulated nutrient for both the malaria parasite and its human host. The importance of the relationship between host iron and the parasite has been underscored recently by studies showing that host iron supplementation may increase the risk of falciparum malaria. It is unclear what host iron sources the parasite is able to access. We developed a flow cytometry-based method for measuring the labile iron pool (LIP) of parasitized erythrocytes using the nucleic acid dye STYO 61 and the iron sensitive dye, calcein acetoxymethyl ester (CA-AM). This new approach enabled us to measure the LIP of P. falciparum through the course of its erythrocytic life cycle and in response to the addition of host serum iron sources. We found that the LIP increases as the malaria parasite develops from early ring to late schizont stage, and that the addition of either transferrin or ferric citrate to culture media increases the LIP of trophozoites. Our method for detecting the LIP within malaria parasitized RBCs provides evidence that the parasite is able to access serum iron sources as part of the host vs. parasite arms race for iron.

| S-EPMC4249674 | biostudies-literature

cAMP signaling regulates DNA hydroxymethylation by augmenting the intracellular labile ferrous iron pool.

Project description:It is widely accepted that cAMP regulates gene transcription principally by activating the protein kinase A (PKA)-targeted transcription factors. Here, we show that cAMP enhances the generation of 5-hydroxymethylcytosine (5hmC) in multiple cell types. 5hmC is converted from 5-methylcytosine (5mC) by Tet methylcytosine dioxygenases, for which Fe(II) is an essential cofactor. The promotion of 5hmC was mediated by a prompt increase of the intracellular labile Fe(II) pool (LIP). cAMP enhanced the acidification of endosomes for Fe(II) release to the LIP likely through RapGEF2. The effect of cAMP on Fe(II) and 5hmC was confirmed by adenylate cyclase activators, phosphodiesterase inhibitors, and most notably by stimulation of G protein-coupled receptors (GPCR). The transcriptomic changes caused by cAMP occurred in concert with 5hmC elevation in differentially transcribed genes. Collectively, these data show a previously unrecognized regulation of gene transcription by GPCR-cAMP signaling through augmentation of the intracellular labile Fe(II) pool and DNA hydroxymethylation.

| S-EPMC5745079 | biostudies-literature

cAMP Signaling Regulates DNA Demethylation by Augmenting the Intracellular Labile Ferrous Iron Pool

Project description:In this study we show that cAMP helps regulate cytosine demethylation through augmenting the intracellular labile ferrous iron pool.

2018-01-01 | GSE101153 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data