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)

Corneas with central epithelial wounds, 3 mm in diameter, were organ cultured in the presence of tunicamycin (TM) (1 microgram/ml), an antibiotic that inhibits glycosylation of asparagine-linked glycoproteins. Compared with control corneas, which healed in 22 hr, corneas cultured in the presence of TM for the entire culture time or for only the first 6 hr displayed a progressively slower epithelial healing rate that essentially dropped to zero by 24 hr of culture time. At 24 hr, approximately 75% of the wound was covered. After repeated washings with TM-free culture media (6X, 10 min each), this effect could consistently be reversed in corneas exposed to TM for 6 hr. Incorporation of [3H]glucosamine into trichloroacetic acid-precipitable proteins of migrating epithelial sheets was reduced to 14% that of controls after 12 hr of culture with TM, whereas [14C]leucine incorporation was not significantly affected. The decreased glycosylation was reflected on the cell surface after 12 and 20 hr culture in the presence of TM: apical cell membranes of the first six cells of the leading edge of the migrating sheet bound significantly fewer ferritin-concanavalin A particles per micrometer of membrane than did controls. These results indicate that synthesis of asparagine-linked glycoproteins is required for continued migration of corneal epithelial sheets. The asparagine-linked glycoproteins that are required for migration probably include cell-surface glycoproteins.
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PMID:Epithelial sheet movement: effects of tunicamycin on migration and glycoprotein synthesis. 669 74

The cell surface of Chlamydia psittaci seems important for establishing infection since (i) UV-treated elementary bodies (EB) attach to and are ingested by L cells and (ii) heat or antibody treatment decreases attachment to L cells and promotes the fusion of chlamydiae-containing phagosomes with lysosomes in macrophages. In the studies reported here, [3H]uridine-labeled UV-treated EB also persisted in mouse resident peritoneal macrophages and L cells, suggesting that phagosome-lysosome fusion is inhibited. We therefore chose to investigate the ingestion and internal fate of isolated purified EB envelopes in both nonprofessional and professional phagocytic cells. EB envelopes are internalized by target host cells as efficiently as are whole EB. Transmission electron microscopy of macrophages whose lysosomes were marked with ferritin revealed the persistence of individual envelopes in phagosomes devoid of ferritin for the 3-h observation period. In contrast, EB envelopes heated to 56 degrees C for 15 min were consistently found in ferritin-labeled phagolysosomes as early as 30 min. As another index of persistence, isolated EB envelopes were radioisotopically labeled with a Bolton-Hunter analog, [3H]N-succinimidyl propionate, and their fate as trichloroacetic acid-precipitable material was followed. A third probe, employed to detect the persistence of non-biodegradable antigen, was indirect immunofluorescence. Fluorescein-positive antigens were brightly visible for 7 days in both macrophages and L cells when they were inoculated with untreated EB or EB maintained in penicillin. But L cells inoculated with EB envelopes or EB treated with UV or chloramphenicol, all of which prevent the conversion of infectious EB into the metabolically active reticulate bodies, displayed reduced internal fluorescence by 2 days and the appearance of fluorescent material on the cell surface. This release of EB envelope material occurred in the absence of phagolysosome fusion. The data add credence to the belief that the spontaneous breakdown or autolytic enzyme release of EB envelope components must occur preparatory to the conversion of EB to reticulate bodies.
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PMID:Chlamydia psittaci elementary body envelopes: ingestion and inhibition of phagolysosome fusion. 684 Aug 60

The uptake of liver ferritin labelled with 125I or 59Fe by guinea-pig reticulocytes has been studied to investigate the characteristics of the uptake process, compare it with transferrin uptake and determine whether ferritin-iron is utilized by the cells in haem synthesis. The results confirmed that guinea-pig reticulocytes, but not mature erythrocytes, take up liver ferritin by a saturable, time- and temperature-dependent process. Up to 70% of the iron taken up by the cells was utilized in haem synthesis and competed directly with iron derived from transferrin. Scatchard analysis of the binding parameters indicated that 30-130 X 10(3) ferritin molecules were bound per cell to high affinity specific membrane receptors (Ka: 1.77 X 10(7) M-1). In contrast, rat took up much less ferritin than guinea-pig reticulocytes and the process was entirely non-specific. Release experiments with guinea-pig reticulocytes at 37 degrees C showed that a maximum of about 70% of the cell-associated 125I-ferritin was released from the cells of which up to 15% was trichloroacetic acid-soluble. We suggest that ferritin uptake by guinea-pig reticulocytes involves receptor-mediated endocytosis. The endocytotic vesicle fuses with a lysosome, iron is removed from the protein and enters a cytosolic pool in which it competes directly with transferrin-derived iron to provide iron for mitochondrial haem synthesis. Some of the ferritin is catabolized and the rest is returned to the extracellular medium during membrane recycling.
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PMID:Ferritin and iron uptake by reticulocytes. 688 88

In this study we used chloroquine to characterize the interalization and lysosomal degradation of receptor-bound 125I-insulin by rat adipocytes and to determine the role of lysosomal processing of insulin in the short-term biologic effects of the hormone. Chloroquine inhibited the degradation of 125I-insulin bound to adipocytes by both association and disslociation experiments. In the former experiments, chloroquine caused a time- and concentration-dependent increase in specifically bound insulin owing to an increase in intact insulin and a decrease in degradation products, as determined by trichloroacetic acid precipitability and gel chromatographic analysis of material extracted from the cells. In the dissociation experiments, 50 microM chloroquine decreased the rate of degradation by two third, as reflected in the release of degradation to or degraded by isolated plasma membranes, on the degradation of 125I-insulin by proteases in the incubation medium, or on the endocytotic uptake of receptor-bound insulin. Quantitative electron miroscopy, using monomeric ferritin-insulin, showed 50 microM chloroquine doubled the number of lysosomal structures containing ferritin. These findings are consistent with an inhibition by chloroquine of lysosomal degradation of internalized receptor-bound insulin. Chloroquine, at these same concentrations, had no effect on the ability of insulin to stimulate glucose transport and oxidation or to inhibit epinephrine-stimulated lipolysis. In these studies, we show that lysosomal degradation of internalized receptor-bound insulin is not necessary for insulin to cause short-term biologic effects in the adipocyte.
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PMID:Lysosomal degradation of receptor-bound 125I-labeled insulin by rat adipocytes: its characterization and dissociation from the short-term biologic effects of insulin. 699 35

The present study provides at least partly answers to some of the questions outlined in the introduction (see also Figs. 2 and 3): Endocytosis and intracellular transport of ferritin, HRP and insulin tracers (125I-insulin, native insulin and insulin-gold) was followed by use of EM-autoradiography, immunocytochemistry and cytochemistry. Proteins are internalized into endocytic vacuoles and transferred to the lysosomes for degradation. Tracers were not transferred to the Golgi apparatus. 125I-insulin is internalized by specific receptor mediated endocytosis from the apical plasma membrane, substantiating the hypothesis that specific endocytosis receptors are responsible for reabsorption of certain proteins. The binding sites are localized in endocytic invaginations and in the microvillus membrane. The binding sites in the invaginations are responsible for endocytosis, whereas the function of the microvilli binding sites is unclear, but they possess the ability to migrate in the plane of the microvillus membrane. Binding to specific binding sites and subsequent internalization of insulin takes place with high efficiency corresponding to more than 50% of the perfused load. Not all proteins are reabsorbed with high efficiency e.g. EGF which has similar molecular weight and pI is shown to be reabsorbed with substantially lower efficiency (about 4%). Binding and absorption efficiency of insulin may also change due to alterations in flow rate and perfused loads of protein: The load determines the magnitude of uptake and the flow rate determines the efficiency in binding and uptake. These changes are suggested to be caused by concomitant changes in the mean luminal concentration. The reabsorption process for insulin is efficient and of large capacity, and is only saturable (Michaelis-Menten kinetics) at very high concentrations of insulin. The proximal tubular internalization and degradation of 125I-insulin reach steady state rapidly. The processing can be described by a two-compartment model with t1/2 for transfer of 125I-insulin to lysosomes of 8.5 min and for lysosomal degradation of 72 min. 125I-PYY a linear peptide with similar molecular weight as EGF and insulin is not endocytosed but extracted with high efficiency (75% removed) by degradation by brush border peptidases and a substantial transtubular transport of TCA-precipitable PYY takes place by a paracellular route. A small vesicular transport of colloidal tracers was demonstrated constituting about 0.5% of the endocytosed amount. A method for covalently cross-linking insulin tracers to apical binding sites is described and evaluated. Recycling of apical binding sites was estimated to be very efficient and did not involve lysosomes or the Golgi apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocytosis in renal proximal tubules. Experimental electron microscopical studies of protein absorption and membrane traffic in isolated, in vitro perfused proximal tubules. 792 57

Increasing non-heme iron concentrations in host tissues are potentially significant, because they can be associated with an increased risk of injury including infections, fibrosis, and neoplasms. We tested the hypothesis that non-heme (Fe3+) in the lung increases with age in both humans and rats. Human tissue was collected at autopsy before fixation occurred. The total number of specimens was 131 with 78 nonsmokers and 53 smokers. Tissue was hydrolyzed in 3 N hydrochloric acid and 10% trichloroacetic acid. Supernatant (Fe3+) was measured with a thiocyanate assay. Non-heme (Fe3+) increased with age in nonsmokers. The correlation coefficient between lung (Fe3+) and age in the nonsmokers was 0.58 (p < 0.0001). Iron stains were negative, whereas those for ferritin demonstrated increased uptake with aging. Smokers had significantly greater non-heme (Fe3+) relative to nonsmokers (101.1 and 46.0 micromol/L respectively; T = 11.44, p < 0.0001). Lung non-heme (Fe3+) in smokers also increased with age (r = 0.75; p < 0.0001). Iron stains demonstrated uptake in the proximity of retained pigmented material. Ferritin stains demonstrated intense uptake in both the macrophages and the airway and alveolar epithelium of smokers. An animal model was also analyzed for an effect of aging on lung non-heme (Fe3+). At specified times between 30 and 186 days of age, rats (n = 48) were anesthetized and exsanguinated, and the lungs were excised. In rats, similar to humans, a positive correlation was seen between lung non-heme (Fe3+) and age (r = 0.73; p = 0.007). Stains for iron in rat lung were uniformly negative, whereas those for ferritin demonstrated increased uptake by airway and alveolar epithelium in older rats. We conclude that non-heme (Fe3+) in lung tissue increases with age in both humans and rats. Elevations in lung non-heme (Fe3+) could contribute to an increased incidence of pneumonias, pulmonary fibrosis, and bronchogenic carcinoma observed among older individuals.
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PMID:Non-heme (Fe3+) in the lung increases with age in both humans and rats. 901 91

Therapeutic iron compounds have limited absorption and often have side-effects, which limits patient compliance. Iron trimaltol is a novel, stable complex, formed between ferric iron (Fe3+) and maltol (3-hydroxy-2-methyl-4-pyrone), and is effective in the treatment of iron deficiency anaemia with few side-effects. However, the kinetics of iron absorption from ferric trimaltol and the reliability of normal colorimetric analysis in detecting iron absorbed from this complex have not been established. We measured increases in serum iron levels in 12 volunteers following oral challenge with four different pharmaceutical formulations of ferric trimaltol in a double-blind, cross-over, randomized study. The conventional colorimetric method for detecting serum iron was compared with thermal analyses after trichloroacetic acid (TCA) treatment of serum. Measurements of serum iron levels by TCA treatment and thermal analysis closely agreed with measurements by colorimetry. For all formulations, serum iron levels peaked at 90 min with a plateau of at least 5 h [mean (standard deviation) peak absorption 8.3% (6.3%) of ingested dose, n=48]. Absorption of iron, based on peak serum values or area under the serum curve, was not different for the four formulations (n=12 each) and correlated with the individual's iron status, as assessed by serum ferritin values (r = -0.6; P < 0.001). Normal colorimetry is suitable for analysis of serum iron levels following ingestion of ferric trimaltol. There is rapid and sustained absorption of iron from ferric trimaltol and, as with ferrous iron, uptake appears to be controlled through normal mechanisms of iron acquisition that depend upon body iron stores.
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PMID:Assessment of iron absorption from ferric trimaltol. 1090 61

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.
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PMID:[Psychiatric manifestations of vitamin B12 deficiency: a case report]. 1502 91

Fe (cellular iron), O (dioxygen, antioxidant inducers, hydrogen peroxide), and P (protein phosphorylation) signals combine to regulate DNA activity (transcription/mRNA synthesis) for antioxidant/Phase II response proteins (e.g., ferritin H, ferritin L, thioredoxin reductase I, NAD(P)H quinone oxido-reductase, heme oxygenase1 and beta-globin) and mRNA activity for proteins of iron transport, storage or oxygen metabolism (e.g., ferritin H, ferritin L, transferrin receptor1, ferroportin, mt-aconitase-TCA cycle and aminolevulinate synthase - heme biosynthesis). Ferritin regulation links the two groups of genetic controls via DNA (ARE-antioxidant response element) and mRNA (IRE-iron responsive element) structures. More is known about the IRE-mRNA and protein repressors, IRPs (iron regulatory proteins/aconitase homologues), than the DNA-ARE and protein repressors, e.g., Bach1. Iron responsive elements are very similar (65-80% sequence identity), but each mRNA has sufficient IRE specificity (>90% phylogenetic sequence conservation), that IRP binding and signal responses vary quantitatively. The structural specificity of each IRE-RNA provides an opportunity for finding small molecule regulators in vitro, and possibly in vivo. The potential of manipulating mRNA function with small molecules targeted to specific RNA regulatory structures, e.g., ferritin mRNA in iron overload, or viral mRNA control structures for replication, is high.
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PMID:Integrating iron and oxygen/antioxidant signals via a combinatorial array of DNA - (antioxidant response elements) and mRNA (iron responsive elements) sequences. 1708 1

Marbling of cattle meat is dependent on the coordinated expression of multiple genes. Cattle dramatically increase their intramuscular fat content in the longissimus dorsi muscle between 12 and 27 months of age. We used the annealing control primer (ACP)-differential display RT-PCR method to identify differentially expressed genes (DEGs) that may participate in the development of intramuscular fat between early (12 months old) and late fattening stages (27 months old). Using 20 arbitrary ACP primers, we identified and sequenced 14 DEGs. BLAST searches revealed that expression of the MDH, PI4-K, ferritin, ICER, NID-2, WDNMI, telethonin, filamin, and desmin (DES) genes increased while that of GAPD, COP VII, ACTA1, CamK II, and nebulin decreased during the late fattening stage. The results of functional categorization using the Gene Ontology database for 14 known genes indicated that MDH, GAPD, and COP VII are involved in metabolic pathways such as glycolysis and the TCA cycle, whereas telethonin, filamin, nebulin, desmin, and ACTA1 contribute to the muscle contractile apparatus, and PI4-K, CamK II, and ICER have roles in signal transduction pathways regulated by growth factor or hormones. The final three genes, NID-2, WDNMI, and ferritin, are involved in iron transport and extracellular protein inhibition. The expression patterns were confirmed for seven genes (MDH, PI4-K, ferritin, ICER, nebulin, WDNMI, and telethonin) using real-time PCR. We found that the novel transcription repressor ICER gene was highly expressed in the late fattening stage and during bovine preadipocyte differentiation. This information may be helpful in selecting candidate genes that participate in intramuscular fat development in cattle.
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PMID:Identification of differentially expressed genes related to intramuscular fat development in the early and late fattening stages of hanwoo steers. 1792 10


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