Hemin-induced DEGs in Lung, Kidney of WT and hepatic SR-BI KO mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE338324 | GEO | 2026/07/15
REPOSITORIES: GEO
Similar Datasets
Project description:Acute hemolysis can deplete haptoglobin and hemopexin, leaving toxic free heme insufficiently controlled. Here, the authors show that scavenger receptor BI (SR-BI) mediates hepatic uptake of free heme and is essential for protection against heme-induced injury and death. Here we examined gene expression post hemin injections
2026-07-24 | E-MTAB-17338 | biostudies-arrayexpress
Project description:Haptoglobin and Hemopexin are plasma acute phase proteins that bind with high affinity hemoglobin and heme, respectively. Several studies have demonstrated that they have a key role in the protection against oxidative stress and inflammation. However, little is known about the functional modules in which they are involved. To gain insights into this issue, we integrated bioinformatic and experimental approaches to identify genes coexpressed with Haptoglobin or Hemopexin and modulated in Haptoglobin and/or Hemopexin knock-out mice. These genes have a high probability to be functionally related to Haptoglobin and/or Hemopexin. Keywords: haptoglobin, hemopexin, microarray, bioinformatics
2006-11-01 | GSE3656 | GEO
Project description:Hemin-induced DEGs in Lung, Kidney of WT and hepatic SR-BI KO mice
| PRJNA1493260 | ENA
Project description:Hemin-induced DEGs in Lung, Kidney of WT and hepatic SR-BI KO mice
| PRJEB121199 | ENA
Project description:Regulatory heme is known to control cellular behavior by regulating the activities of hemoproteins. We hypothesized that increased levels of regulatory heme may drive T cell exhaustion. To test this, we first confirmed that treatment with hemin, a heme analog, effectively increased intracellular regulatory heme levels in T cells. To evaluate the transcriptional changes in CD8+ T cells treated with hemin, we conducted RNA sequencing on CD8+ T cells with and without exogenous hemin treatment. The RNA-seq data revealed that hemin treatment strongly modulated gene expression patterns associated with terminally exhausted T cells. Pathway enrichment analysis further revealed that hemin suppressed pathways involved in proliferation and cytokine production while altering metabolic processes, such as cholesterol efflux and fatty acid biosynthesis, which are known to regulate T cell function. These results suggest that increased levels of regulatory heme drive T cell exhaustion differentiation.
2026-01-25 | GSE312103 | GEO
Project description:The mechanistic links between hemoglobin oxidation, heme release, and neuronal death after intracerebral hemorrhage are incompletely defined. Using organotypic brain-slice cultures (BSCs) that model the RBC-toxin cascade, we dissect how the scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) interrupt this pathology. BSCs exposed to free hemoglobin, heme, or their complexes (HbHp, hemeHpx) reveal that both Hb and heme drive iron-dependent neuronal injury, while Hp and Hpx confer protection by distinct mechanisms. Multi-modal readouts – including iron quantification, lipid peroxidation, neuronal apoptosis, and RNA-seq – demonstrate that Hpx abolishes toxicity by sequestering heme, whereas Hp stabilizes Hb and enables Nrf2-dependent cytoprotective gene expression. These data quantitatively map how Hp and Hpx reroute hemolytic toxicity toward resilience.
2025-12-29 | GSE299269 | GEO
Project description:Haptoglobin and Hemopexin are plasma acute phase proteins that bind with high affinity hemoglobin and heme, respectively. Several studies have demonstrated that they have a key role in the protection against oxidative stress and inflammation. However, little is known about the functional modules in which they are involved. To gain insights into this issue, we integrated bioinformatic and experimental approaches to identify genes coexpressed with Haptoglobin or Hemopexin and modulated in Haptoglobin and/or Hemopexin knock-out mice. These genes have a high probability to be functionally related to Haptoglobin and/or Hemopexin. We performed a gene expression analysis of the livers of Hp- and/or Hx-null mice compared to wild-type controls. The mice used in the following experiments, i.e. wild-type (Hp+/Hx+/), Hp-null (Hp-/-Hx+/), Hx-null (Hp+/Hx-/-), and HpHx-null (Hp-/-Hx-/-), were littermates derived by breeding F1 double heterozygous Hp+/-Hx+/- mice in the mixed genetic background C57/BLJ6 X 129Sv. We have three experimental points: Hx-null mice, Hp-null mice and HpHx-null mice. At least 5 adult mice per genotype were perfused via aorta with PBS, sacrificed and their liver pooled. Thirty microgram of total RNA were subjected to direct labeling reaction by incorporation of cyanin 3 (Cy3) or cyanin 5 (Cy5) fluorescent dyes into the cDNA by priming with oligo(dT). Four replicates were set up for each experimental point. In order to exclude artifacts resulting from different dye usage, we employed the dye-swap approach.
2006-10-31 | E-GEOD-3656 | biostudies-arrayexpress
Project description:This research provides novel insights into the underlying mechanism whereby the cyto- and neuro-protective heme binding protein hemopexin can be inactivated by reactive nitrogen species generated during the heme- and cytokine- driven inflammation that accompanies hemolysis. Nitration of amino acids is generally considered a selective and specific effect reflecting biological events. As we describe in a summary in the next paragraph, three tyrosine resides are preferentially targeted that reside in the heme binding site of apo-hemopexin. Hemopexin deficiency states develop in clinical sepsis and such modifications of hemopexin that we have identified and describe could also provide evidence-based guidance to physicians when heme toxicity is driving pathology to assess the timing and extent of hemopexin replenishment therapies and the patient responses to such treatment.
2016-12-13 | MSV000080394 | MassIVE
Project description:Heme, an iron-containing prosthetic group found in many proteins, carries out diverse biological functions such as electron transfer, oxygen storage and enzymatic reactions. Hemin, the oxidised form of heme, is used to treat porphyria and also to activate heme-oxygenase (HO) which catalyses the rate-limiting step in heme degradation. Our group has previously demonstrated that hemin displays antitumor activity in breast cancer (BC). The aim of this work has been to study the effect of hemin on protein expression modifications in a BC cell line to gain insight into the molecular mechanisms of hemin antitumor activity. For this purpose, we carried out proteome analysis by Mass Spectrometry (MS) which showed that 1309 proteins were significantly increased in hemin-treated cells, including HO-1 and the proteases that regulate HO-1 function, and 921 proteins were significantly decreased. Furthermore, the MS-data analysis showed that hemin regulates the expression of heme- and iron- related proteins, adhesion and cytoskeletal proteins, cancer signal transduction proteins and enzymes involved in lipid metabolism. By biochemical and cellular studies, we further corroborated the most relevant in-silico results. Altogether, these results show the multiple physiological effects that hemin treatment displays in BC and demonstrate its potential as anticancer agent.
2023-07-20 | PXD036701 | Pride
Project description:Hemoglobin (Hb) released from red blood cells during hemolysis is a trigger of oxidative vascular damage with endothelial cells being a primary target. The Hb and heme scavenger proteins haptoglobin (Hp) and hemopexin (Hx) have been characterized as a sequential defense system with Hp as the primary protector and Hx as a backup when all Hp is depleted during more severe or prolonged hemolysis. The paradigm of sequential protection by the two scavengers is based on observational patient data proposed by Mueller-Eberhardt. In this study we present a mechanistic rationale for these clinical observations using a novel in vitro model of Hb triggered endothelial damage. We identified oxyHb(Fe2+) transformation to ferric Hb(Fe3+), free heme transfer from ferric Hb(Fe3+) to lipoprotein and subsequent oxidative reactions in the lipophilic phase. The accumulation of toxic lipid peroxidation products liberated during oxidation reactions lead to endothelial damage characterized by a specific gene expression pattern, reduced cellular ATP and monolayer disintegration. Quantitative analysis of key biochemical and functional parameters allowed us to precisely define the mechanisms and concentrations required for Hp and Hx to prevent this toxicity. In the case of Hp we defined an exponential relationship between Hp availability relative to oxyHb(Fe2+) and related protective activity. This exponential relationship demonstrates that large Hp quantities are required to prevent Hb toxicity. In contrast, the linear relationship between Hx concentration and protective activity allows for significant protection by the backup scavenger during conditions of large excess of free oxyHb(Fe2+) that occurs when all Hp is consumed. The diverse protective function of Hp and Hx in this model can be explained by the different target specificities of the two proteins.
2018-02-25 | GSE66283 | GEO