Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.
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PMID:Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation. 2419 59

Iron is bound to mobile transferrin (TF) and ferritin in blood. TF receptors (TFRC and TFR2) regulate intracellular iron by delivering iron from TF into the cytoplasm. In this study, we examined the effects of 10 single nucleotide polymorphisms (SNPs) in each of the genes for TF and TF receptors on blood iron concentrations in Japanese subjects. Blood iron levels were determined by microwave plasma-atomic emission spectrometry and the SNPs were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Blood iron levels in males were significantly higher than those in females. Therefore, the analysis was performed only in males. Blood iron concentrations did not correlate with age and postmortem intervals in males. Among the 10 SNPs in TF, TFRC, and TFR2 genes, significant associations were observed between TF genotypes (rs12769) and male iron concentrations. Individuals with genotype GG in rs12769 had significantly higher blood iron concentrations than those with GA. Previous studies have shown the association between high tissue iron concentrations and disease, liver iron levels are higher in infants dying from sudden infant death syndrome and decreased blood iron concentrations were observed in critically ill children. Therefore, rs12769 in TF might be related to diseases and mortality risk.
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PMID:Association of SNPs in transferrin and transferrin receptor genes with blood iron levels in human. 3031 34

Iron is essential for physical activity due to its role in energy production pathways and oxygen transportation via hemoglobin and myoglobin. Changes in iron-related biochemical parameters after physical exercise in athletes are of substantial research interest, but molecular mechanisms such as gene expression are still rarely tested in sports. In this paper, we evaluated the mRNA levels of genes related to iron metabolism (PCBP1, PCBP2, FTL, FTH, and TFRC) in leukocytes of 24 amateur runners at four time points: before, immediately after, 3 h after, and 24 h after a marathon. We measured blood morphology as well as serum concentrations of iron, ferritin, and C-reactive protein (CRP). Our results showed significant changes in gene expression (except for TFRC), serum iron, CRP, and morphology after the marathon. However, the alterations in mRNA and protein levels occurred at different time points (immediately and 3 h post-run, respectively). The levels of circulating ferritin remained stable, whereas the number of transcripts in leukocytes differed significantly. We also showed that running pace might influence mRNA expression. Our results indicated that changes in the mRNA of genes involved in iron metabolism occurred independently of serum iron and ferritin concentrations.
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PMID:Changes in Serum Iron and Leukocyte mRNA Levels of Genes Involved in Iron Metabolism in Amateur Marathon Runners-Effect of the Running Pace. 3120 55

Background: Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-methyladenosine (m6A) modification has expanded the realm of previously undiscovered post-transcriptional gene regulation mechanisms in eukaryotes. Many studies have demonstrated that m6A methylation represents a distinct layer of epigenetic deregulation in carcinogenesis and tumor proliferation. However, the status of m6A modification and iron metabolism in HPSCC remains unknown. Methods: Bioinformatics analysis, sample analysis, and transcriptome sequencing were performed to evaluate the correlation between m6A modification and iron metabolism. Iron metabolic and cell biological analyses were conducted to evaluate the effect of the m6A reader YTHDF1 on HPSCC proliferation and iron metabolism. Transcriptome-wide m6A-seq and RIP-seq data were mapped to explore the molecular mechanism of YTHDF1 function in HPSCC. Results: YTHDF1 was found to be closely associated with ferritin levels and intratumoral iron concentrations in HPSCC patients at Sir Run Run Shaw Hospital. YTHDF1 induced-HPSCC tumorigenesis depends on iron metabolism in vivo in vitro. Mechanistically, YTHDF1 methyltransferase domain interacts with the 3'UTR and 5'UTR of TRFC mRNA, then further positively regulates translation of m6A-modified TFRC mRNA. Gain-of-function and loss-of-function analyses validated the finding showing that TFRC is a crucial target gene for YTHDF1-mediated increases in iron metabolism. Conclusion: YTHDF1 enhanced TFRC expression in HPSCC through an m6A-dependent mechanism. From a therapeutic perspective, targeting YTHDF1 and TFRC-mediated iron metabolism may be a promising strategy for HPSCC.
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PMID:YTHDF1-enhanced iron metabolism depends on TFRC m6A methylation. 3320 30