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)

To facilitate an understanding of the molecular events associated with vascular smooth muscle cells (SMC) growth arrest and differentiation, we have isolated a number of cDNAs encoding mRNAs that are more abundantly expressed in high density growth-arrested SMC. From 40,000 recombinant plaques, we identified 6 cDNA clones which encoded genes more highly expressed in density-arrested SMC. DNA sequence analysis of a cDNA clone which hybridized to a 5.5-kilobase mRNA revealed a 96% sequence homology to the carboxyl-terminal propeptide region of the human alpha 2(I) collagen gene. Sequence analysis of 3 other cDNA clones which all recognized a 1-kilobase mRNA, indicated that they encode the ferritin H-chain subunit gene. The large increase in ferritin H-chain mRNA expression was both growth arrest and high density-dependent, but did not appear to be cell-cell contact-dependent. The increase in H-chain was partially accounted for by an increase in the transcription of this gene, but a post-transcriptional mechanism likely accounts for the majority of the observed difference in mRNA level. A greater than 3-fold higher expression of ferritin H-chain mRNA was also observed in BC3H1s (a nonfusing myogenic cell line) during the process of differentiation, but no elevation in ferritin H-chain mRNA was associated with density-dependent growth arrest in fibroblasts. Hemin (an intracellular iron donor) induced an elevation in ferritin H-chain mRNA expression in both preconfluent and post-confluent SMC, but was unable to elevate the preconfluent mRNA level to an untreated postconfluent level. In addition, deferoxamine (an intracellular iron chelator) was unable to reduce the ferritin mRNA level in postconfluent SMC. These results suggest that high density growth arrest-mediated elevation in ferritin H-chain occurs by a mechanism distinct from that induced by an increase in intracellular iron. cAMP was also a powerful modulator of the expression of ferritin H-chain gene since cells treated with forskolin or dibutyryl cAMP had a 5-7-fold higher level of ferritin H-chain mRNA. We propose that the increase in the ferritin H-chain mRNA level in postconfluent SMC may occur through a cAMP-dependent pathway and may be associated with an enhanced differentiated phenotype.
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PMID:Increased ferritin gene expression is both promoted by cAMP and a marker of growth arrest in rabbit vascular smooth muscle cells. 165 64

Fragments of the rat ferritin-H 5'-flanking region up to 1 kilobase in length were generated by the polymerase chain reaction using FRTL5 rat thyroid cell genomic DNA as template. Ferritin-H 5'-flanking region fragments of 219, 351, 666, and 1046 basepairs (bp), ligated up-stream to the reporter gene luciferase, were transiently transfected into FRTL5 thyroid cells and NIH-3T3 mouse fibroblasts. In both cell types, constitutive (nonstimulated) ferritin-H promoter activity increased progressively with constructs containing increasing lengths of 5'-flanking region. TSH or (Bu)2cAMP (dBcAMP) stimulation of FRTL5 cells transfected with the shorter (219 and 351 bp) ferritin-H 5'-flanking region fragments increased promoter activity 2- to 3-fold. However, with the longer DNA segments (666 and 1046 bp), the extent of TSH stimulation was less. Exposure of transfected NIH-3T3 cells to dBcAMP mimicked in all respects the effects of TSH and dBcAMP on ferritin-H promoter activity in FRTL5 cells. Transcription initiation sites in the luciferase reporter gene were unaffected by the length of the ferritin-H 5'-flanking region included in the construct or by dBcAMP stimulation. Plasmid constructs with 45 bp of the ferritin-H 5'-flanking region containing a potential cAMP response element did not reveal any promoter activity or dBcAMP responsiveness in this region. Gel shift mobility assays with the -219 bp ferritin-H 5'-flanking region fragment and NIH-3T3 nuclear proteins revealed specific protein-DNA interaction. Reduced DNA mobility was inhibited by excess unlabeled probe DNA, but not by DNA fragments corresponding to the recognition sites for a variety of known trans-activating factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyrotropin and adenosine 3',5'-monophosphate stimulate the activity of the ferritin-H promoter. 196 70

We examined the effect of thyrotropin (TSH) stimulation of FRTL5 rat thyroid cells on ferritin H mRNA levels. On Northern blot analysis, TSH (in the presence of serum and insulin) increased ferritin H mRNA levels, with an initial response evident after 1 h of stimulation. Ferritin H mRNA levels increased approximately 4-fold over basal levels after 4 h of TSH stimulation and showed little increase thereafter, maintaining a plateau for up to 48 h of TSH stimulation. Inducers of cAMP also increased ferritin H mRNA levels in FRTL5 cells to about the same extent, but the rate of response was not as rapid as with TSH stimulation. In serum-poor medium without insulin, the TSH effect was considerably weaker, increasing only about 2-fold after 24 h of stimulation. Also in serum-poor medium, insulin-like growth factor-I alone had a weak stimulatory effect on ferritin H mRNA levels. TSH and insulin-like growth factor-I had additive effects under these conditions. Nuclear run-on transcription assays were performed using nuclei prepared from FRTL5 cells. In serum-containing medium, TSH increased the transcriptional activity of ferritin H mRNA 3-4-fold without an increase in beta-actin transcriptional activity. The kinetics of TSH stimulation of ferritin H transcriptional activity were similar to the cellular ferritin H mRNA response to TSH stimulation. Dibutyryl-cAMP (dB-cAMP) increased ferritin H transcriptional activity about 4-fold, but not as rapidly as did TSH stimulation. In summary, our data indicate that ferritin H mRNA levels in FRTL5 thyroid cells are transcriptionally regulated by both TSH and dBcAMP stimulation. These data contrast with the predominantly nontranscriptional regulation of ferritin H mRNA levels observed in other tissues. The difference in the kinetics of the response to TSH and dBcAMP is consistent with the concept that not all effects induced by TSH stimulation of thyroid cells are mediated by cAMP as a second messenger.
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PMID:Transcriptional regulation of ferritin H messenger RNA levels in FRTL5 rat thyroid cells by thyrotropin. 215 9

The interaction of LH and its receptor was investigated by ultrastructural analysis of ferritin-LH (FELH) binding to isolated rat luteal cells in the absence and presence of prostaglandin F2 alpha (PGF2 alpha), an inhibitor of LH-stimulated cAMP production. FELH, with a molar ratio of FE to LH of 1:1, bound specifically to LH receptors, either singly or in small groups (microaggregates), at intervals on luteal cell surfaces. FELH elicited a dose-dependent increase in progesterone production, and its binding increased with increased FELH concentration. The number of LH receptors per cell, estimated from particle counts, was about 6.2 +/- 0.6 X 10(4), similar to estimates from Scatchard analysis of [125I]iodo-hCG binding. Microaggregate size increased in parallel with FELH binding. Only partial aggregation was seen at concentrations of FELH that elicited near-maximal progesterone secretion. Aggregation continued to increase at FELH concentrations beyond that required to elicit maximal progesterone secretion. In the presence of PGF2 alpha, FELH-stimulated progesterone production was attenuated, and FELH binding decreased from 2.9 +/- 0.4 X 10(4) to 2.1 +/- 0.3 X 10(4) receptors/cell. PGF2 alpha did not alter microaggregate size on cells labeled with FELH at 4 C when membrane fluidity was already reduced, but did substantially reduce microaggregate size at 37 C. We conclude that FELH binds initially at random sites on membranes of isolated luteal cells and that as binding increases, receptors aggregate into small groups. Furthermore, microaggregates are related in part to receptor occupancy and possibly also to levels of cAMP or activation of the adenylate cyclase mechanism.
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PMID:Luteinizing hormone (LH) receptor aggregation: modification of ferritin-LH binding and aggregation by prostaglandin F2 alpha and ferritin-LH. 609 54

The Y-1 murine adrenal and CCL43 rat Leydig tumor cell lines were used as model systems for studying the role of tubulin in steroidogenesis. Prior to the stimulation of steroidogenesis it was observed that most of the tubulin present in these cells, as determined by indirect immunofluorescence, was in a 0.2-0.6 micrometers dia. granular form. When these cells were treated with ACTH and cAMP, respectively, it was observed that the granular form of tubulin was replaced by many organized microtubules. These granules were identified in the electron microscope using tubulin antibody/ferritin localization and appeared to be membrane-bound and identical to structures previously described as containing cholesterol. We have isolated these structures using cell homogenization and sucrose gradient centrifugation and analyzed the steroid composition by thin layer chromatography (94% cholesterol, 6% cholesterol ester). These granules also contained tubulin as determined by gel electrophoresis. In addition, they contained acid phosphatase as determined by their ability to hydrolize beta-glycerolphosphate. We suggest that tubulin may be involved in the sequestering of cholesterol by preventing its transport to the mitochondria where conversion to pregnenolone takes place, and that steroidogenesis is increased when tubulin is dissociated from the cholesterol granules.
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PMID:The role of tubulin in the steroidogenic response of murine adrenal and rat Leydig cells. 627 35

The goal of this study was to synthesize biotinylated derivatives of alprenolol, a beta-adrenergic antagonist, and to determine whether these ligands could bind simultaneously to both avidin (a biotin-binding protein) and to the beta-adrenergic receptor. Such ligands would be useful for beta-adrenergic receptor localization and purification, since avidin can be covalently labelled with fluorescent or electron-dense markers or can be linked to solid supports for affinity chromatography. Three biotinyl derivatives of alprenolol were synthesized and characterized. Each derivative bound to avidin and also possessed high affinity for the duck erythrocyte beta-adrenergic receptor. Two of the compounds, biotinyl-caproyl-cysteaminyl-alprenolol (BCCA) and biotinyl-dodecanoyl-cysteaminyl-alprenolol (BDCA) had the same affinities for the duck erythrocyte beta-adrenergic receptor (membrane-bound or digitonin-solubilized) in the absence and presence of avidin. This indicated that high affinity complexes could be formed between the beta-adrenergic receptor and avidin using these bifunctional biotinyl-alprenolol ligands. In contrast, biotinyl-cysteaminyl-alprenolol (BCA), in which the distance between the biotin and alprenolol moieties was shorter, had greatly reduced affinity for the duck erythrocyte beta-adrenergic receptor in the presence of avidin. Additional studies showed that BDCA, avidin-BDCA, and ferritin-avidin-BDCA were equally potent in inhibiting the isoproterenol stimulation of cAMP accumulation in intact HeLa cells. The data reported in this paper demonstrate the importance of an appropriate spacer sequence to allow correct apposition of the receptor and avidin molecules, and suggest that BDCA may be a useful probe for beta-adrenergic receptor localization and purification.
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PMID:Formation of complexes between avidin and beta-adrenergic receptors using biotinyl-alprenolol derivatives. 631 49

We used co-cultures of porcine ovarian granulosa cells and mouse adrenocortical tumor cells (Y-1) to examine the kinetics of contact-dependent intercellular signal transfer and to assess the molecular mechanisms employed by this process. Exposure to follicle-stimulating hormone (FSH) caused cAMP-dependent protein kinase dissociation in granulosa cells and, with time, in Y-1 cells if, and only if, they contacted a responding granulosa cell. Y-1 cells close to a granulosa cell but not touching it failed to respond similarly. In reciprocal experiments, co-cultures were stimulated with adrenocorticotropic hormone (ACTH). Y-1 cells dissociated protein kinase as did granulosa cells in contact with Y-1 cells; however, granulosa cells that were not in contact with Y-1 cells failed to respond to the hormone. Fluorogenic steroids were secreted by Y-1 cells cultured alone and stimulated with ACTH, but were not secreted by cultures exposed to FSH. Neither hormone caused fluorogenic steroid production by granulosa cells. On the other hand these steroids were secreted in co-cultures stimulated with ACTH and to a lesser degree in co-cultures exposed to FSH. Autoradiography revealed that I125-FSH bound only to granulosa cells, never to Y-1 cells, even if they were in contact with an ovarian cell. The possibility of cell fusion was tested by experiments in which Y-1 cell membranes were labeled with cationized ferritin. These cells were then placed in co-culture with ovarian granulosa cells that had previously been allowed to ingest latex spheres. At regions of gap junctions between Y-1 and granulosa cells ferritin remained attached to the adrenal cell membrane and was never observed to migrate to the granulosa cell membrane. From these data, we conclude that hormone specific stimulation of one cell type leads to protein kinase dissociation in heterotypic partners only if they contact a hormone responsive cell. This signal transfer is bidirectional, exhibits temporal kinetics and occurs in the absence of apparent cell fusion. The only structural feature connecting Y-1 and granulosa cells were gap junctions implying they provided the communication channels; however, alternative mechanisms cannot be excluded. We have not established the identity of the signal being transferred although cAMP is a logical candidate.
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PMID:Hormone-induced intercellular signal transfer dissociates cyclic AMP-dependent protein kinase. 632 20

The expression of thyroglobulin and other thyroid-specific markers depends upon the activation of protein kinase A (PKA) by cyclic AMP. A rat thyroid cell line dedifferentiates when transformed with Ki-ras oncogene. The decrease in thyroglobulin gene expression parallels a reduction in the level of PKA nuclear catalytic subunit. We find that the activity of cAMP-responsive elements and thyroglobulin promoters is down-regulated in Ras-transformed cells. Transcription of a third cAMP-regulated gene, H-ferritin, is similarly reduced. cAMP-responsive element and H-ferritin expression were stimulated when intracellular cAMP levels were increased. Reactivation of the thyroglobulin promoter required depletion of PKC in addition to increased cAMP. We also find that v-Ras activation leads to a significant increase in membrane-bound PKC. These data support the idea that v-Ras via PKC inhibits the transmission of cAMP-PKA signals to the nucleus. We suggest that the thyroglobulin promoter is more sensitive than other cAMP-dependent promoters to reduced nuclear levels of PKA catalytic subunit.
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PMID:Ki-ras oncogene interferes with the expression of cyclic AMP-dependent promoters. 771 89

The synthesis of heat-shock proteins (HSPs) and other stress proteins, including heme oxygenase (HO) and ferritin, is differentially induced by heat and oxidizing agents. In order to determine what role cAMP plays in those inductions in human monocytes-macrophages (m phi), we used cAMP activators or analogues alone or in combination with various stressful conditions. A stimulation in cAMP production did not per se affect stress proteins synthesis in m phi but modulated their induction in a differential way according to the stimulus. cAMP increased the synthesis of HSPs after heat shock. During erythrophagocytosis, whereas cAMP depressed the phagocytic process and the associated generation of superoxide anions, it enhanced the synthesis of HSPs, while inhibiting that of HO and ferritin. These results indicate that cAMP has a direct enhancing effect on the expression of stress proteins controlled by a classic heat-shock promoter, while decreasing their expression when induced by oxidative stress.
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PMID:cAMP modulates stress protein synthesis in human monocytes-macrophages. 792 3

Biological studies have not yet provided direct evidence for a link between electromagnetic fields (EMFs) and cancer. The hypotheses I present here describes ferritin as a direct pathway for the EMF-cancer link, which is supported by previous studies: (a) Ferritin plays a very important role in its associated cancers. (b) Iron is the principal regulator of ferritin synthesis and ferritin gene expression is induced by signals including hormones and cAMP. (c) Preliminary biological studies have demonstrated that EMFs induce some cellular effects including changes in hormone levels, alterations in cell membranes, variations of intracellular cAMP and even the modification of protein synthesis. So, it is reasonable to link the biological effects of EMFs with ferritin gene expression and ferritin synthesis which are mainly regulated by iron, hormones and cAMP and eventually the EMF-cancer link.
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PMID:EMF-cancer link: the ferritin hypothesis. 823 75


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