Expression Of Ferritin Heavy Chain Research Articles

Ferritin May Mediate SIN-1-Induced Protection against Oxidative Stress

In porcine aortic endothelial cells, a 20-h incubation with hydrogen peroxide (0.5 mm) markedly reduced the number of viable cells. A 6-h preincubation with linsidomine (SIN-1, 0.5 mm) protected endothelial cells from hydrogen peroxide-dependent cytotoxicity and increased the surviving endothelial cell fraction by 85%. This protection was associated with a 2.5-fold induction of ferritin heavy chain mRNA and ferritin protein by SIN-1. The nitric oxide donor glyceryl trinitrate was also found to induce transcriptional and translational expression of ferritin heavy chain. A protective effect comparable to SIN-1 was observed when preincubating the cells with iron-free apoferritin (1 mg/ml). These findings suggest that ferritin induction, presumably via release of nitric oxide, may be a mechanism underlying long-term cytoprotection by SIN-1 against oxidative stress.

Differential expression of ferritin Heavy chain in a rat transitional cell carcinoma progression model

To identify molecular markers with predictive value for the progression of superficial bladder cancer we used the differential hybridization analysis approach. Since primary tumor material is heterogeneously composed of subpopulations that are poorly characterized, we used in this study a rat progression model system that phenotypically and cytogenetically resembles human superficial bladder cancer. In the differential hybridization analysis we compared the mRNA populations of low and high metastatic tumor lines. We observed an overexpression of ferritin Heavy chain (ferritin H) in the tumor line with the lower metastatic capacity and better differentiated phenotype. The exact clinical relevance for the differential expression of ferritin H in human bladder cancer remains to be determined.

Ferritin heavy chain is a progesterone-inducible marker in the uterus during pregnancy.

The female sex steroid, progesterone, plays a central role in mammalian pregnancy by regulating crucial events in the uterus such as transformation of endometrium for implantation and maintenance of pregnancy. The hormone acts through its specific nuclear receptor and modulates the functions of target cells by controlling the synthesis of specific proteins. The identity of genes that are regulated by progesterone in the uterus during various phases of pregnancy, however, remains largely unknown. In this study, we employed a differential gene-screening method to identify the gene encoding ferritin heavy chain (FHC), a component of the multisubunit iron-binding protein ferritin, as being regulated by progesterone in the uterus. We observed that uterine expression of the FHC messenger RNAs (mRNAs) rose dramatically at the onset of pregnancy, coincident with the surge of progesterone. FHC expression continued at this elevated level throughout gestation when the progesterone concentration remained high. At term, FHC expression declined sharply as the progesterone concentration dropped. We localized FHC proteins exclusively in uterine stromal cells, a major site of action of progesterone during pregnancy. Administration of mifepristone, an antiprogestin, during the early stages of pregnancy abolished both FHC mRNA and protein expression, clearly suggesting a primary role of progesterone in the regulation of this gene. Consistent with this scenario, administration of progesterone to ovariectomized animals after a brief estrogen priming led to a marked (25-fold) induction of FHC mRNA in the uterus, whereas estrogen, dexamethasone, or dihydrotestosterone had no effect. Based on these results, we propose that FHC is a novel and useful marker to study progesterone-regulated events in the uterus during pregnancy.

Ferritin heavy chain is a progesterone-inducible marker in the uterus during pregnancy

The female sex steroid, progesterone, plays a central role in mammalian pregnancy by regulating crucial events in the uterus such as transformation of endometrium for implantation and maintenance of pregnancy. The hormone acts through its specific nuclear receptor and modulates the functions of target cells by controlling the synthesis of specific proteins. The identity of genes that are regulated by progesterone in the uterus during various phases of pregnancy, however, remains largely unknown. In this study, we employed a differential gene-screening method to identify the gene encoding ferritin heavy chain (FHC), a component of the multisubunit iron-binding protein ferritin, as being regulated by progesterone in the uterus. We observed that uterine expression of the FHC messenger RNAs (mRNAs) rose dramatically at the onset of pregnancy, coincident with the surge of progesterone. FHC expression continued at this elevated level throughout gestation when the progesterone concentration remained high. At term, FHC expression declined sharply as the progesterone concentration dropped. We localized FHC proteins exclusively in uterine stromal cells, a major site of action of progesterone during pregnancy. Administration of mifepristone, an antiprogestin, during the early stages of pregnancy abolished both FHC mRNA and protein expression, clearly suggesting a primary role of progesterone in the regulation of this gene. Consistent with this scenario, administration of progesterone to ovariectomized animals after a brief estrogen priming led to a marked (25-fold) induction of FHC mRNA in the uterus, whereas estrogen, dexamethasone, or dihydrotestosterone had no effect. Based on these results, we propose that FHC is a novel and useful marker to study progesterone-regulated events in the uterus during pregnancy.