Effects of iron overload on primary hepatocyte of WT and Fxr-/- mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE161863 | GEO | 2023/11/20
REPOSITORIES: GEO
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Project description:Effects of iron overload on primary hepatocyte of WT and Fxr-/- mice
| PRJNA679732 | ENA
Project description:Fusobacterium nucleatum (F. nucleatum) contributes to the development of colorectal cancer (CRC) by inducing chronic inflammation. We found that iron deposition in macrophages is associated with poor prognosis of CRC patients with high amount of F. nucleatum. To explore the impact of iron on macrophage properties in the presence of F. nucleatum, we conducted RNA sequencing of THP-1 macrophages pretreated with ferric anmonium citrate (FAC) or deferoxamine (DFO), followed by treatment with F. nucleatum. Several chemokine genes were differentially increased in FAC-treated cells when compared with DFO-treated cells, suggesting that iron is required for the efficient induction of tumor-promoting chemokines in macrophages upon F. nucleatum infection. Our results suggest a prognostic role for iron in F. nucleatum-positive CRC.
2022-08-21 | GSE192400 | GEO
Project description:Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (a PPAR- antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR- functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.
2023-10-02 | GSE243891 | GEO
Project description:In plasma, iron is normally bound to transferrin, but in conditions of iron overload when the iron-binding capacity of transferrin is exceeded, non-transferrin-bound iron (NTBI) appears in plasma. NTBI is taken up by hepatocytes and other parenchymal cells via NTBI transporters and can cause cellular damage by promoting the generation of reactive oxygen species. However, how NTBI affects endothelial cells, the most proximal cell type exposed to circulating NTBI, has not been explored. We modeled in vitro the effects of systemic iron overload on endothelial cells by treating primary human umbilical vein endothelial cells (HUVECs) with NTBI (ferric ammonium citrate, FAC). Using an unbiased approach, we showed by RNA-Seq that iron loading alters lipid homeostasis in HUVECs by inducing SREBP2-mediated cholesterol biosynthesis. We also determined that FAC increased the susceptibility of HUVECs to apoptosis induced by TNFα. Moreover, we showed that cholesterol biosynthesis contributes to iron-potentiated apoptosis. Treating HUVECs with a cholesterol chelator hydroxypropyl-β-cyclodextrin demonstrated that depletion of cholesterol was sufficient to rescue HUVECs from TNFa-induced apoptosis, even in the presence of FAC. Finally, we showed that FAC or cholesterol treatment modulated the TNFα pathway by inducing novel proteolytic processing of TNFR1 to a short isoform that localizes to lipid rafts. Our study raises the possibility that iron-mediated toxicity in human iron overload disorders is at least in part dependent on alterations in cholesterol metabolism in endothelial cells, increasing their susceptibility to apoptosis.
2021-09-01 | GSE168534 | GEO
Project description:Identified genes deregulated in mouse primary hepatocytes after modulation of expression/activity of FOXA2 and FXR in glucagon or insulin state
2018-08-16 | GSE113549 | GEO
Project description:We investigated transcriptional response of CaCo-2 cells to iron treatments, we studied hemin effect by adding hemin to DMEM-FBS medium and iron deficiency effects in using an iron free medium compared to the same supplemented with FAC (ferric ammonium citrate). Experiment Overall Design: Biological replicates were used (3 samples) of each iron treatments (SF-FAC, SF-0, DMEM-FBS, DMEM-Hemin). Each sample was labelled with cy5 and a pool of each sample was constituted and labelled with cy3.
2008-01-19 | E-GEOD-3573 | biostudies-arrayexpress
Project description:We investigated transcriptional response of CaCo-2 cells to iron treatments, we studied hemin effect by adding hemin to DMEM-FBS medium and iron deficiency effects in using an iron free medium compared to the same supplemented with FAC (ferric ammonium citrate). Keywords: various iron treatment, differential gene expression, hemin treatment, iron-free
2006-07-14 | GSE3573 | GEO
Project description:Farnesoid X receptor (FXR) plays a prominent role in hepatic lipid metabolism. The FXR gene encodes four proteins with structural differences suggestive of discrete biological functions about which little is known. We show that FXR isoforms have specific effects on hepatic metabolism and uncover novel pathways under their control. Gene expression profiling of hepatocytes expressing each FXR variant revealed large differences in their target gene sets. Notably, FXRα2 (but not α1) activates a broad transcriptional program in hepatocytes conducive to lipolysis, fatty acid oxidation, and ketogenesis. Consequently, FXRα2 decreases cellular lipid accumulation and improves insulin sensitivity. FXRα2 expression in Fxr-/- mouse liver activates a similar gene program and robustly decreases hepatic triglyceride levels. On the other hand, FXRα1 reduces hepatic triglyceride content to a lesser extent and does so through regulation of lipogenic gene expression. Bioenergetic cues, such as fasting and exercise, dynamically regulate Fxr splicing in mouse liver to increase Fxrα2 expression. Our results show that the main FXR variants in human liver (α1 and α2) reduce hepatic lipid accumulation through distinct mechanisms and to different degrees. Thus, pharmacological or lifestyle interventions, such as exercise, aimed at modulating hepatic FXR splicing may improve the therapeutic efficacy of FXR agonists.
2015-09-28 | GSE73035 | GEO
Project description:Vibrio vulnificus multiply rapidly in host tissues under iron overloaded conditions. To understand the effects of iron in the physiology of this pathogen we performed a genome-wide transcriptional analysis of this bacterium growing under three different iron concentrations. V.vulnificus CMCP6 cells were grown under three different iron concentrations (TSBS + EDDA 50uM, TSBS and TSBS + FAC 250 ug/ml) and samples taken at log phase. Keywords: Response to the iron concentration of the media
2008-08-07 | GSE10633 | GEO
Project description:Vibrio vulnificus multiply rapidly in host tissues under iron overloaded conditions. To understand the effects of iron in the physiology of this pathogen we performed a genome-wide transcriptional analysis of this bacterium growing under three different iron concentrations. V.vulnificus CMCP6 cells were grown under three different iron concentrations (TSBS + EDDA 50uM, TSBS and TSBS + FAC 250 ug/ml) and samples taken at log phase. Keywords: Response to the iron concentration of the media Strains were grown to an OD600nm of 0.6 to 0.8 in TSBS, TSBS with the addition of 250 μg/ml FAC or TSBS with the addition of 50 μM EDDA. Three independent cultures of the V. vulnificus cells grown in each media, were combined and treated as a single sample for the RNA extraction to minimize culture variation. Two samples per condition were used for the microarray analysis. Cells were centrifuged and the pellets resuspended in RNAWiz reagent (Ambion®, Austin, TX). Total RNA was extracted from each strain according to the manufacturerâ??s instructions
2010-05-25 | E-GEOD-10633 | biostudies-arrayexpress