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)

Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. A randomized, double-blind trial was performed to define precisely the tissue-specific thyromimetic actions of tiratricol. Ten athyreotic patients, treated for thyroid carcinoma, were randomly assigned to receive L-T4 sodium 0.7 micrograms/kg daily and either tiratricol 10 micrograms/kg or placebo twice daily. The daily dose of L-T4 was increased by 25-50 micrograms increments until the TRH-stimulated TSH level was less than 0.1 mU/L. After measurement of biochemical and physiological parameters of thyroid hormone actions, patients crossed treatment groups. Patients required 46% less L-T4 to achieve equivalent TSH suppression when taking tiratricol. Hepatic effects were enhanced by tiratricol administration, with significant increases in sex hormone binding globulin and ferritin concentrations, 14% and 37%, respectively. Levels of serum cholesterol, LDL cholesterol, and apolipoprotein B were reduced by 7%, 10%, and 13%, respectively, during tiratricol therapy. Triglyceride levels also declined, but there were no changes of high density lipoprotein cholesterol or apolipoproteins AI and AII. Resting metabolic rate, body weight, urea nitrogen excretion, and symptoms did not differ between the two treatment regimens. Cardiovascular function, as reflected by mean arterial pressure and pulse wave arrival time, was not different during tiratricol therapy. Skeletal metabolic activity was affected by tiratricol, with marked elevation of osteocalcin without significant change in serum calcium, PTH, and urinary calcium and hydroxyproline excretion. Tiratricol has increased hepatic and skeletal actions of potential therapeutic value, but does not have enhanced thyromimetic activity specific to the pituitary gland.
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PMID:Organ-specific effects of tiratricol: a thyroid hormone analog with hepatic, not pituitary, superagonist effects. 151 83

Iron absorption by intestinal epithelial cells, passage onto plasmatic apotransferrin, and regulation of the process remain largely misunderstood. To investigate this problem, we have set up an in vitro model, consisting in CaCo2 cells (a human colon adenocarcinoma line, which upon cultivation displays numerous differentiation criteria of small intestine epithelial cells). Cells are cultivated in a serum-free medium, containing 1 microgram/ml insulin, 1 ng/ml epidermal growth factor, 10 micrograms/ml albumin-linoleic acid, 100 nM hydrocortisone, and 2 nM T3 on new, transparent, Cyclopore polyethyleneterephthalate microporous membranes coated with type I collagen. Cells rapidly adhere, grow, and form confluent monolayers; after 15 days, scanning electron microscopy reveals numerous uniform microvilli. Domes, which develop on nonporous substrata, are absent on high porosity membranes. Culture medium from upper and lower compartments of microplate inserts and cell lysates were immunoprecipitated after labeling with [3H]glucosamine and leucine; analysis was done by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by autoradiography. [3H]transferrin is found mainly in the lower compartment and in cells; [3H]apolipoprotein B is released in both compartments, and fibronectin almost entirely recovered in the lower compartment; [3H]transferrin receptors and ferritin are only present in cell lysates. Binding experiments also show that transferrin receptors are accessible from the lower compartment. These results suggest that CaCo2 cells, cultivated in synthetic medium on membranes of appropriate porosity, could provide an in vitro model of the intestinal barrier, with the upper compartment of the culture insert corresponding to the apical pole facing the intestinal lumen and the lower one to the basal pole in contact with blood.
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PMID:Iron absorption by intestinal epithelial cells: 1. CaCo2 cells cultivated in serum-free medium, on polyethyleneterephthalate microporous membranes, as an in vitro model. 183 Mar 3

The concentration of cholesterol, apolipoproteins A-I, B, and E has been determined in lymphedema fluid from nine patients with chronic primary lymphedema. The concentrations were: 38.14 +/- 21.06 mg/dl for cholesterol, 15.6 +/- 6.17 mg/dl for apolipoprotein A-I, 7.5 +/- 2.8 mg/dl for apolipoprotein B, and 1.87 +/- 0.50 mg/dl for apolipoprotein E. These values represent 23%, 12%, 6%, and 38% of plasma concentrations, respectively. The ratio of esterified to unesterified cholesterol in lymphedema fluid was 1.46 +/- 0.45. Lipoproteins of lymphedema fluid were fractionated according to particle size by gradient gel electrophoresis and by exclusion chromatography. Gradient gel electrophoresis showed that a majority of high density lipoproteins (HDL) of lymphedema fluid were larger than ferritin (mol wt 440,000) and smaller than low density lipoproteins (LDL); several discrete subpopulations could be seen with the large HDL region. Fractionation by exclusion chromatography showed that more than 25% of apolipoprotein A-I and all of apolipoprotein E in lymphedema fluid was associated with particles larger than plasma HDL2. Apolipoprotein A-I also eluted in fractions that contained particles the size of or smaller than albumin. Isolation of lipoproteins by sequential ultracentrifugation showed that less than 25% of lymphedema fluid cholesterol was associated with apolipoprotein B. The majority of apolipoprotein A-containing lipoproteins of lymphedema fluid were less dense than those in plasma. Ultracentrifugally separated fractions of lipoproteins were examined by electron microscopy. The fraction d less than 1.019 g/ml contained little material, while fraction d 1.019-1.063 g/ml contained two types of particles: round particles 17-26 nm in diameter and square-packing particles 13-17 nm on a side. Fractions d 1.063-1.085 g/ml had extensive arrays of square-packing particles 13-14 nm in size. Fractions d 1.085-1.11 g/ml and fractions d 1.11-1.21 g/ml contained round HDL, 12-13 nm diameter and 10 nm diameter, respectively. Discoidal particles were observed infrequently.
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PMID:Human lymphedema fluid lipoproteins: particle size, cholesterol and apolipoprotein distributions, and electron microscopic structure. 408 43

We hypothesized that the formation of foam cells and fatty streaks requires a postsecretory oxidative modification of lipoproteins that targets them for rapid uptake by macrophages. Lipid peroxidation may in part depend on the concentration of tissue iron, one of the major oxidants in vivo. We analyzed the relation between sonographically assessed carotid atherosclerosis and body iron stores in a population sample of 847 men and women aged 40 to 79 years. In a logistic regression analysis adjusting for age, sex, and all major vascular risk markers, ferritin emerged as one of the strongest indicators of carotid artery disease in both sexes (40 to 59 years; odds ratio, 1.54 per 100 micrograms/L; P < .001). The predictive significance of ferritin was found to be synergistic with that of hypercholesterolemia. Variations in body iron stores between sexes may partly explain evident sex differences in the expression of carotid atherosclerosis. In the elderly (> or = 60 years) the predictive significance of ferritin was found to decrease parallel to that of apolipoprotein B. The current study suggests a possible role of body iron in early atherogenesis.
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PMID:Body iron stores and presence of carotid atherosclerosis. Results from the Bruneck Study. 791 13

The metabolism of low density lipoprotein (LDL) oxidized with phorbol myristate acetate (PMA) stimulated neutrophils plus ferritin (LDLox) by human monocyte-derived macrophage (HMDM) was studied. Binding of 125I-labeled LDLox to HMDM and further uptake and degradation were higher than for native 125I-labeled LDL. LDLox seems to be taken up by HMDM through the scavenger receptor as indicated by competition studies with unlabeled native and autoxidized LDL. An increased concentration of cellular cholesteryl esters was observed in HMDM exposed to LDLox. Oxidative modification of LDL increased its electrophoretic migration on agarose gel and also the fragmentation of apolipoprotein B. Data suggest that LDLox is incorporated by human macrophages and can potentially induce foam-cell formation.
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PMID:Human macrophage metabolism of low density lipoprotein oxidized by stimulated neutrophils and ferritin. 798 Jun 92

Elevated serum ferritin concentrations between 200 and 500 microg/l have been found to be a strong risk factor for acute myocardial infarction in Finnish men, but the reason for this association is still uncertain. In the Finnish population ferritin concentrations correlated with factors of insulin resistance syndrome. As these factors have been found to be associated with an LDL subfraction phenotype of increased concentrations of small, dense LDL particles, we hypothesized an association between ferritin and an atherogenic LDL subfraction profile, a finding which could be an explanation for the observed relationship between ferritin and atherosclerosis. Therefore we determined serum ferritin levels, metabolic cardiovascular risk factors, and the LDL subfraction phenotype in 93 healthy men without signs for infection or coronary heart disease. We found that men with moderately elevated ferritin levels (200-500 microg/l; n = 31) had a significantly worse coronary risk profile than men with lower levels ( < 200 microg/l; n = 62). Elevated ferritin concentrations were associated with significantly higher values for serum triglycerides, VLDL cholesterol, VLDL apolipoprotein B (P < 0.01), IDL cholesterol, fasting glucose (P < 0.05) and uric acid (P < 0.01), and lower levels for HDL2b and HDL2a cholesterol and apolipoprotein A-I (P < 0.05), and lipoprotein(a) (P < 0.01). Elevated ferritin levels were, however, not associated with an unfavourable LDL subfraction profile of increased concentrations of small, dense LDL particles.
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PMID:Relationship of serum ferritin concentrations with metabolic cardiovascular risk factors in men without evidence for coronary artery disease. 905 Jul 80

Insulin and lipid metabolism were studied in seven patients (19+/-1 years) with end-stage renal disease on continuous cycling peritoneal dialysis (CCPD) before and after 6 months of therapy with human recombinant erythropoietin (EPO) to correct anemia. Hematocrit increased from 22.2+/-1.8% to 34.8+/-1.8% (P<0.001) following EPO treatment. Serum ferritin (P<0.05) and serum iron (P<0.01) decreased significantly after anemia correction. There were no significant differences in the height, weight, anthropometric measures, or intakes of protein and total calories in the patients before and after the 6 months of EPO therapy. There were no differences in serum biochemical parameters, including 1,25-dihydroxyvitamin D3 and parathyroid hormone in these patients before and after 6 months of EPO therapy. Residual renal function and Kt/Vurea were also not different before and after 6 months of EPO therapy. The hyperinsulinemic euglycemic clamp technique was used to measure insulin sensitivity. Before EPO, insulin sensitivity was low in patients on CCPD (238+/-19 mg/m2 per min) compared with controls (320+/-30; P<0.01). After 6 months of EPO therapy, insulin sensitivity increased by 28% (305+/-26, P<0.01 vs. pre-EPO values), so that these values were no longer different from control values. The hyperglycemic clamp technique was used to measure insulin secretion. Before EPO, both early- and late-phase insulin secretion were elevated in patients on CCPD compared with controls (P<0.01 in both cases). These indices of insulin secretion decreased significantly (P<0.01) following 6 months of EPO. Before EPO, plasma triglycerides, total cholesterol, low-density lipoprotein, cholesterol, and apolipoprotein B were elevated in patients compared with controls. These lipid concentrations decreased significantly following 6 months of EPO. Thus, treatment of anemia by EPO is associated with improvements in insulin and lipid abnormalities in uremic patients on CCPD.
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PMID:Metabolic effects of erythropoietin in patients on peritoneal dialysis. 981 91

The biogenesis of apolipoprotein B is quite complex in view of its huge size, hydrophobicity, obligate association with lipids such as cholesterol and triglycerides prior to secretion, and intracellular degradation of a substantial proportion of newly synthesized molecules. Multiple proteins likely serve roles as molecular chaperones to assist in folding, assembly with lipids, and regulation of the secretion of apolipoprotein B. In these studies, we developed a strategy to isolate proteins associated with apolipoprotein B in rat livers. The purification consisted of two stages: first, microsomes were prepared from rat liver and treated with chemical cross-linkers, and second, the solubilized proteins were co-immunoprecipitated with antibody against apolipoprotein B. We found that several proteins were cross-linked to apolipoprotein B. The proteins were digested with trypsin, and the released peptides were sequenced by tandem mass spectrometry. The sequences precisely matched 377 peptides in 99 unique proteins. We show that at least two of the identified proteins, ferritin heavy and light chains, can directly bind apolipoprotein B. These and possibly other proteins identified by this proteomic approach are novel candidates for proteins that affect apolipoprotein B during its biogenesis.
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PMID:A proteomic approach identifies proteins in hepatocytes that bind nascent apolipoprotein B. 1193 86

Cardiovascular diseases connected with atherosclerosis are the main factor of morbidity and mortality in patients with end-stage renal failure. Hyperhomocysteinemia is a known and independent risk factor of atherosclerosis, occurring in 85-95% patients treated with hemodialysis. The aim of this study was to analyse relation between plasma level of homocysteine and chosen indicators of atherosclerosis development and also examined retrospectively cardiovascular complications in these patients. The study was carried out in 100 patients on hemodialysis who were divided into two groups: 72 patients with mild (20.74 mumol/l +/- 3.75) and 28 patients with moderate hyperhomocysteinemia (38.81 mumol/l +/- 9.81). Ultrasonographic examinations of Carotid Communis Artery Intima-Media Thickness (IMT), Ankle-Arm Blood Pressure Index (AABPI), echocardiographic parameters and biochemical examinations such as: PTH, folic acid and Vitamin B12, total protein, albumin, fibrinogen, glucose, total, LDL and HDL cholesterol, transferring, apolipoprotein B, lipoprotein (a), sodium potassium, calcium, phosphate, magnesium, iron, ferritin, urea, creatinine, uric acid and value of Hb, Ht, total iron binding capacity and transferring saturation, were performed. Patients with hypertension were divided into groups according to the number of taken anti-hypertensive drugs. Hyperhomocysteinemia was confirmed in 96% of patients. Frequency and type of acute cardiovascular complications were not related with the level of hyperhomocysteinemia. Statistically significant difference between IMT and level of hyperhomocysteinemia was observed. In patients with mild hyperhomocysteinemia IMT was 0.68 mm +/- 0.24 whereas in patients with moderate hyperhomocysteinemia 0.80 mm +/- 0.25, p < 0.036). Positive correlation between level of homocysteine and IMT (r = 0.22, p < 0.03) was noted. Based on this study, we concluded, that measurement of intima-media thickness is a good indicator of atherosclerosis development and correlates with hyperhomocysteinemia in patients on maintenance hemodialysis. It clearly confirms the role of hyperhomocysteinemia as significant risk factor of atherosclerosis in those patients.
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PMID:[Hyperhomocysteinemia and advancement of atherosclerosis in patients with chronic renal failure on maintenance hemodialysis]. 1273 67

Apolipoprotein B is secreted with atherogenic lipids as lipoprotein particles from hepatocytes. Regulation of the secretion of apolipoprotein B is largely post-translational and reflects the balance between processes that leads to particle assembly or to intracellular degradation. Previously, we conducted a proteomic screen to find proteins that bind apolipoprotein B in rat liver microsomes. We identified ferritin heavy and light chains in this screen among other proteins and showed that the two ferritins bind apolipoprotein B directly in vitro. In hepatocytes and other cells, ferritin heavy and light chains form cytosolic cages that store iron. We now show that ferritin heavy or light chains post-translationally inhibit the secretion of apolipoprotein B without altering the export of other hepatic proteins including albumin, factor XIII, and apolipoprotein A-I. This inhibition of apolipoprotein B secretion is not due to diminished lipid synthesis and can be partially overcome by stimulating triglyceride synthesis. The block in apolipoprotein B secretion by ferritins leads to an increase in endoplasmic reticulum-associated degradation of the apolipoprotein. Thus, despite being cytosolic proteins without known chaperone activity, ferritins can specifically regulate the secretion of apolipoprotein B post-translationally. The metabolic pathways for iron storage and intercellular cholesterol and triglyceride transport could intersect.
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PMID:Ferritins can regulate the secretion of apolipoprotein B. 1281 58


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