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)

The effect of the microtubular inhibitor colchicine, administered at either 0.036 (dose 1) or 5 mumol/kg (dose 2), on hepatic ferritin uptake was determined over a 5-h period of ferritin infusion in normal and iron-loaded rats. In the absence of colchicine, the serum ferritin concentration of normal rats was reduced after 5 h to 20 +/- 9% and in iron-loaded rats to 30 +/- 1% of the expected values, indicating ferritin clearance. After colchicine (dose 1), a similar result was observed in normal rats; however, in iron-loaded rats, an increase in serum ferritin to 77 +/- 16% of the expected value indicated a decreased ferritin clearance and/or increased ferritin release. The administration of the higher dose to normal rats also resulted in an increase in serum ferritin to 72 +/- 2% of the expected value. In iron-loaded rats, after dose 2 the ferritin concentration rose to 359 +/- 108% of the expected value, consistent with the release of endogenous ferritin. Colchicine administration had no effect on biliary ferritin in normal rats; however, in iron-loaded rats, both doses resulted in a fivefold increase in the release of biliary ferritin. The results suggest that ferritin uptake is facilitated by receptor-mediated endocytosis, which is partially inhibited by colchicine. Release of ferritin also occurs as a result of colchicine administration, and this is dependent on both the dose of colchicine and the iron status of the animal.
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PMID:Effect of colchicine on the clearance of ferritin in vivo. 233 98

An established and validated method using loops of intestine in vivo in rats was used to study the effects of cytoskeletal inhibitors on iron absorption. Radioactive iron instilled into the loop of intestine pretreated with test substance was monitored in the blood and, after death, ferritin loading with radioactive iron was measured on density gradients of mucosal cell homogenates and absorbed iron in the carcass was determined. Colchicine, vincristine and cytochalasin B all caused dose- and time-dependent inhibition of iron absorption, and the effects of cytochalasin B were reversible within 1 h. It is not known which cellular component is the vehicle for the transcellular movement of iron from the intestinal lumen onto plasma transferrin; however, this study showed that the uptake of iron by ferritin in an iron-absorbing loop of intestine paralleled the actual absorption of iron into the carcass. This phenomenon did not occur in non-iron-absorbing intestinal and was inhibited by the action of the cytoskeletal inhibitors in the iron-absorbing region. Previously we had shown that iron uptake into cells and onto cellular transferrin was virtually the same throughout the small intestine, irrespective of the iron-absorbing capacity of the region. The results of this study therefore suggest that iron absorption depends on an intact cytoskeletal system and that ferritin in the iron-absorbing cell is able to load from the pool of iron committed to transcellular movement onto plasma transferrin.
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PMID:The effects of cytoskeletal inhibitors on intestinal iron absorption in the rat. 406 90

Thioglycollate-elicited mouse peritoneal macrophages were cultivated in vitro and endocytosis of native and cationized horseradish peroxidase was studied electron microscopically and biochemically. Native peroxidase (HRP) was ingested by fluid-phase endocytosis and accumulated in lysosomes. Cationized peroxidase (CHRP) bound diffusely to the macrophage surface in a saturable manner. It was then internalized via membrane folds and transferred not only to lysosomes but also to the Golgi complex, mainly those parts referred to as GERL and positive for acid phosphatase activity. Following initial uptake, surface staining for CHRP was lost, although the tracer remained present in the medium. This indicates that anionic binding sites were internalized together with the ligand and not immediately replaced. Accordingly, continued uptake of CHRP occurred at a rate similar to that for HRP. Exposure of the macrophages to cationized ferritin (CF) decreased their ability to bind CHRP. However, after 2 to 4 h in CF-free medium, the CHRP-binding ability returned and raised to 2 to 3 times higher values than in cells not exposed to CF. Treatment with cycloheximide at a concentration that effectively inhibits protein synthesis did not clearly affect this regeneration. These findings support the concept of recirculation of plasma membrane constituents. They further suggest that there exists an intracellular membrane pool which rapidly exchanges with the cell surface. Colchicine removed cytoplasmic microtubules, caused a characteristic disorganization of the Golgi complex, and inhibited uptake of both HRP and CHRP. Additionally, no transport of CHRP to the Golgi complex or GERL was observed in colchicine-treated cells. The regeneration of surface anions after exposure to CF was also delayed. Contrarily, lumicolchicine was without effect on cell morphology and uptake as well as intracellular transport of the tracers. Nevertheless, the effects of colchicine on endocytosis were not necessarily due to a direct role of microtubules. They could be secondary to a disturbed function of the Golgi complex or other organelles after collapse of the microtubular cytoskeleton.
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PMID:Endocytosis of native and cationized horseradish peroxidase by cultured mouse peritoneal macrophages. Variations in cell surface binding and intracellular traffic and effects of colchicine. 733 93

The aim of this study was to evaluate the incidence of anemia detected in familial Mediterranean fever (FMF) and the effect of disease activity and colchicine therapy along with interleukins to laboratory tests, including serum transferrin receptor (TfR), in the diagnosis of anemia seen in FMF in children. After detecting anemia in 63.4% of 172 FMF patients followed up by our rheumatology outpatient polyclinics, it was decided to study 3 groups of patients: group 1, 17 newly diagnosed FMF patients; group 2, 36 FMF patients on colchicine therapy; and group 3, 17 healthy children as control for the symptom of anemia. All 3 groups of patients were investigated for their hematological parameters, iron status, including soluble transferrin receptor (sTFR) concentrations and sTFR index, and IL-6 levels. Anemia ratio was 9/17, 53%; 11/36, 31%; and 1/17, 5% in the groups 1, 2 and 3, respectively. There was a significant difference between hemoglobin (Hb) values in the first group and the second (patients who were on colchicine therapy). Furthermore, in the second group there was a significant difference between the Hb concentrations at the time of diagnosis and after colchicine therapy (p = .003). There was a positive correlation between Hb and plasma iron and transferrin saturation in group 1 and disease beginning age, iron, transferrin saturation, and erythrocyte sedimentation rate (ESR) in the second group. In the first group the anemic patients' iron and transferrin saturation were significantly lower than normal, while ferritin levels were higher. In the second group, a good correlation was found with ESR and Hb levels; the higher ESR values were detected in patients with lower Hb values. Of the anemic and nonanemic patients of the first and second groups, values for interleukin 6 and iron parameters, including sTFR, were found similar. Anemia detected in FMF patients was found related to iron status more than interleukins. Colchicine therapy had a positive effect on anemia as well as on disease activity. Resolution of symptoms of FMF occurred with correction of the anemia, if the patient ESR values also decreased on colchicine therapy.
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PMID:The anemia of familial Mediterranean fever disease. 1625 Nov 71

We present here a case of an asymptomatic end-stage renal disease (ESRD) patient, who had an unexplained persistent mild leukocytosis in the setting of an extremely high ferritin level (8,997 ng/ml; reference range: 12 - 300 ng/ml) 3 weeks after she suffered from a myocardial infarction (MI). Infection as the cause of these laboratory abnormalities was ruled out. A week later, the patient was noted to have asymptomatic hypotension (100/60 mmHg; her baseline blood pressure was 120/70 mmHg) during a maintenance hemodialysis session. An echocardiography revealed an interval development of moderate pericardial effusion when compared to her previous echocardiography 4 weeks before. In the setting of a recent MI with other laboratory markers suggesting an ongoing inflammatory process, a tentative diagnosis of Dressler's syndrome was made. A pericardial tap yielded exudative (bloody) fluid, thus, confirming our suspicion. Dressler's syndrome results from an inflammation of the pericardium as a consequence of an underlying autoimmune process few weeks to months after a myocardial infarction or post-cardiac surgery. Although it typically presents with pleuritic chest pain, fever, leukocytosis, and a friction rub; our case illustrates that the initial presentation may be asymptomatic in ESRD patients. For the same reason, it is likely an under-recognized entity in such patients. An unexplained elevated ferritin in an ESRD patient with recent history of MI should prompt an investigation for Dressler's syndrome. In those with associated significant pericardial effusion, daily HD should be initiated and anticoagulation should be avoided. Unlike other ESRD associated pericarditis, steroids and NSAIDs should be avoided in Dressler's syndrome as they may hamper cardiac remodeling in the immediate post-MI period. Colchicine may offer some benefit in patients with associated chest pain. For those failing medical management or manifesting overt signs of tamponade, surgical drainage should be preferred.
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PMID:Extremely high ferritin level after an acute myocardial infarction in an end stage renal disease patient. 2321 38