Disease relevance of FTH1

• A genomic phage clone containing a full-length copy of a functional human gene for ferritin heavy chain has been isolated [1].
• This mechanism may have been adapted by breast cancer cells over expressing PLIF [2].
• Previously, we found that the insect midgut, a main site of iron load, is also a primary site of ferritin expression and that, in the yellow fever mosquito, Aedes aegypti, the expression of the ferritin heavy-chain homologue (HCH) is induced following blood feeding [3].
• Accumulation and translation of ferritin heavy chain transcripts following anoxia exposure in a marine invertebrate [4].
• Cloning and sequencing of an Escherichia coli K12 gene which encodes a polypeptide having similarity to the human ferritin H subunit [5].

High impact information on FTH1

• In studying the changes that occur in concanavalin A-activated T lymphocytes, an mRNA species was discovered by hybridization of poly(A)+ mRNA with a human ferritin heavy chain cDNA probe [6].
• The heavy-subunit family (FTH) includes 15-20 genes and/or pseudogenes; the light-subunit family (FTL) includes at least three genes [7].
• FTH/BamHI localizes to chromosome 3, is biallelic, and has a heterozygosity frequency of .39, a minor allele frequency of .33, and a polymorphic information content (PIC) of .34 [7].
• We have also identified and characterized two genetic polymorphisms: FTH/BamHI and FTH/TaqI [7].
• The gene that encodes the human ferritin heavy chain has been transfected into mouse fibroblasts [8].

Biological context of FTH1

• Iron regulatory proteins (IRPs) 1 and 2 post-transcriptionally control mammalian iron homeostasis by binding to iron-responsive elements (IREs), conserved RNA stem-loop structures located in the 5'- or 3'-untranslated regions of genes involved in iron metabolism (e.g. FTH1, FTL, and TFRC) [9].
• We describe here a third ferritin-related subunit cloned from human placenta cDNA library and named PLIF (placental immunomodulatory ferritin) [2].
• PLIF protein was found to localize in syncytiotrophoblasts of placentas (8 weeks of gestation) at the fetal-maternal interface [2].
• In contrast to FTH, PLIF mRNA does not include the iron response element in the 5'-untranslated region, suggesting that PLIF synthesis is not regulated by iron [2].
• This additional sequence shows 94.1%, 62.5%, and 58.9% identity to the 3' flanking sequence of the human liver and mouse and rat FTH genomic clones, respectively [10].

Anatomical context of FTH1

• Biochemical analyses of these bodies isolated from the striatum and cerebellar cortex revealed that ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH1) were the main constituents [11].
• The functionality of the gene was demonstrated by the fact that both transient transfectants and stable transformants of murine fibroblasts actively transcribe human ferritin heavy-chain mRNA [1].
• Increased levels of PLIF transcript and protein were also detected in the breast carcinoma cell lines T47D and MCF-7 but not in the benign corresponding cell line HBL-100 [2].
• METHODS: The in vitro effect of PLIF/C48 was tested in mixed lymphocyte cultures (MLCs) of allogeneic mouse splenocytes [12].
• The differential PLIF-C48 effects (i.e., myeloid progenitor cell growth and T-cell suppression) are due to their effect on the cytokine-chemokine networks [13].

Associations of FTH1 with chemical compounds

• Tumor necrosis factor-alpha and interleukin 1-alpha regulate transferrin receptor in human diploid fibroblasts. Relationship to the induction of ferritin heavy chain [14].
• Furthermore, after CXCL12 treatment, FHC underwent time-dependent nuclear translocation and phosphorylation at serine residues [15].
• By contrast, a mutant form of FHC in which serine 178 was replaced by alanine (S178A) failed to undergo phosphorylation, suggesting that serine 178 is the major phosphorylation site [15].
• The ferritin H subunit has a potent ferroxidase activity that catalyses the oxidation of ferrous iron, whereas ferritin L plays a role in iron nucleation and protein stability [16].
• Using a refined pulsed laser photolysis/pulsed laser-induced fluorescence (PLP/PLIF) technique, the kinetics of the reaction of a surrogate three-ring polynuclear aromatic hydrocarbons (PAH), anthracene (and its deuterated form), with hydroxyl (OH) radicals was investigated over the temperature range of 373 to 1200 K [17].

Other interactions of FTH1

• We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to protect cells from oxidative damage [18].
• We report the cloning of the previously uncharacterized FTH sequence from 6p (FTHL15) and show that it is probably a processed pseudogene [19].
• A depot x background interaction for osteonectin (P < 0.01) and ferritin heavy chain (P = 0.03) gene expression was observed for steers slaughtered after grazing, indicating that nutritional management can affect gene expression in adipose tissue depots differently [20].
• Osteonectin, ferritin heavy chain, and decorin gene expression was greater (P < 0.05) in s.c. than in i.m. adipose tissue of finished steers [20].
• Suppression of ROS by NF-kappaB is mediated by Ferritin heavy chain (FHC)--the primary iron-storage mechanism in cells--and possibly, by the mitochondrial enzyme Mn++ superoxide dismutase (Mn-SOD) [21].

Analytical, diagnostic and therapeutic context of FTH1

• In vitro, PLIF was shown to down-modulate mixed lymphocyte reactions and to inhibit the proliferation of peripheral blood mononuclear cells stimulated with OKT3 [2].
• Northern blot analyses of the poly(A)+ RNAs from human brain and liver, using a human brain ferritin heavy chain (FTH) cDNA as the probe, shows the presence of two transcripts of 1.4 and 1.1 kb [10].
• Sequence analysis also suggests a differential poly(A) site selection in the production of FTH mRNA in FB and liver [22].
• Recombinant PLIF-C48 exhibited cell-mediated immunosuppression [13].
• Blocking of PLIF activity by vaccination of mice with C48 prior to mating inhibited pregnancy development [23].

References