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 role of the manganese (Mn) oxidation state on cellular Mn uptake and toxicity is not well understood. Therefore, undifferentiated PC12 cells were exposed to 0-200 microM Mn(II)-chloride or Mn(III)-pyrophosphate for 24 h, after which cellular manganese levels were measured along with measures of cell viability, function, and cytotoxicity (trypan blue exclusion, medium lactate dehydrogenase (LDH), 8-isoprostanes, cellular ATP, dopamine, serotonin, H-ferritin, transferrin receptor (TfR), Mn-superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD) protein levels). Exposures to Mn(III) >10 microM produced 2- to 5-fold higher cellular manganese levels than equimolar exposures to Mn(II). Cell viability and ATP levels both decreased at the highest Mn(II) and Mn(III) exposures (150-200 microM), while Mn(III) exposures produced increases in LDH activity at lower exposures (> or =50 microM) than did Mn(II) (200 microM only). Mn(II) reduced cellular dopamine levels more than Mn(III), especially at the highest exposures (50% reduced at 200 microM Mn(II)). In contrast, Mn(III) produced a >70% reduction in cellular serotonin at all exposures compared to Mn(II). Different cellular responses to Mn(II) exposures compared to Mn(III) were also observed for H-ferritin, TfR, and MnSOD protein levels. Notably, these differential effects of Mn(II) versus Mn(III) exposures on cellular toxicity could not simply be accounted for by the different cellular levels of manganese. These results suggest that the oxidation state of manganese exposures plays an important role in mediating manganese cytotoxicity.
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PMID:Manganese oxidation state mediates toxicity in PC12 cells. 1592 12

The phosphate carrier (PiC) catalyses the import of phosphate into mitochondria where it is needed for ATP synthesis. We have analysed the 5'-flanking region of the human PiC gene and found that it has a single transcriptional initiation site and lacks a TATA box. Through deletion analysis of the -1213/-25 nt region, we identified an activation domain (-223/-25) and an inhibition domain (-1017/-814). The most effective promoter activity in transfected HeLa cells corresponded to the region containing putative binding sites for Sp1 (-163/-142; where Sp1 stands for stimulating protein-1) and CREB (-138/-116; where CREB stands for cAMP-response-element-binding protein). These DNA sequences were active in gel-shift assays in the presence of HeLa cell nuclear extracts or recombinant Sp1 and CREB respectively. Forskolin increased PiC promoter activity via the CREB site. Both footprinting and transfection of deletion constructs of the inhibition region (-1017/-814) showed that PiC silencer activity extends over 25 nt (-943/-919), which specifically binds two proteins present in HeLa cell nuclear extracts. These transcription factors were purified by DNA affinity, analysed by MS and identified as p54(nrb)/NonO (nuclear RNA binding protein) and PSF (protein-associated splicing factor). The PiC silencer region cloned in front of the ferritin promoter conferred a strong inhibition to the heterologous promoter. These findings may provide insight into control of PiC gene expression in different cell types and under different growth conditions. To our knowledge, this is the first study to analyse the regulation of the PiC gene expression in any cell.
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PMID:Functional analysis of the promoter of the mitochondrial phosphate carrier human gene: identification of activator and repressor elements and their transcription factors. 1598 30

It is well known that reduced peak oxygen uptake (peak VO2) is a predictor for mortality in several chronic diseases and during the preoperative period. The aim of this study was to investigate the factors that influence peak VO2 in renal transplant candidates receiving continuous ambulatory peritoneal dialysis (CAPD) therapy. We included 22 chronic renal failure patients (12 men, 10 women; ages 29.64 +/- 8.29 years; CAPD duration, 37.35 +/- 7.15 months) in this study. Pulmonary function tests and symptom-limited cardiopulmonary exercise tests were administered to all patients. Cardiopulmonary exercise tests were performed on a cycle ergometry at the same time of day for all patients. We analyzed the exercise duration, maximum work rate, and peak VO2 level during cycle ergometry. Serum hemoglobin, hematocrit, total cholesterol, triglyceride, blood urea nitrogen, creatinine, albumin, prealbumin, C-reactive protein, sedimentation rate, ferritin, sodium, potassium, parathyroid hormone, calcium, and phosphorus levels were analyzed from samples. Mean values of exercise duration (6.86 +/- 1.56 minutes), peak VO2 (17.20 +/- 4.91 mL/min/kg), and maximum work rate (77.09 +/- 26.09 watts) were lower when we compared them with predicted values for a healthy population. Peak VO2 was well correlated with serum phosphorus levels (4.51 +/- 1.28 mg/dL, r = .592, P = .004). Test duration was correlated with peak VO2 (r = .489, P = .025) and serum phosphorus levels (r = .530, P = .024). There were no significant correlations with other factors. As a component of ATP, phosphorus is at the hub of the energy-related mechanisms operative in muscles of the respiratory and musculoskeletal systems. Therefore, we suggest that low exercise capacity might be related to low serum phosphorus levels, and that optimal control of serum phosphorus therapy would increase exercise capacity, exercise duration, and oxygen consumption resulting in a decrease of postoperative mortality in renal transplantation candidates.
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PMID:Factors affecting exercise capacity in renal transplantation candidates on continuous ambulatory peritoneal dialysis therapy. 1654 31

We have visualized directly the distribution of the cytochrome b(6)/f and coupling factor ATP synthetase complexes in thylakoid membranes of embedded, thin-sectioned, intact chloroplasts by using rabbit antibodies directed against each complex, followed by ferritin-conjugated goat anti- (rabbit immunoglobulin G) antibodies. The labeling patterns indicate that in spinach (Spinacia oleracea) chloroplasts the cytochrome b(6)/f complex is distributed laterally throughout both stacked grana and unstacked stroma membrane regions, whereas the coupling factor ATP synthetase complex is found exclusively in stroma thylakoids and in the marginal and end membranes of grana.
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PMID:Lateral Distribution of the Cytochrome b(6)/f and Coupling Factor ATP Synthetase Complexes of Chloroplast Thylakoid Membranes. 1666 97

Studies have shown that hepatitis C (HCV) is associated with type 2 diabetes mellitus (DM2) possibly due to insulin resistance and inflammation. Metabolic syndrome is a risk factor for DM2. Our objectives were to assess the relationship between HCV and metabolic syndrome and inflammatory markers. We used data from The Third National Health Nutrition and Examination Survey (NHANES-III). We excluded pregnant women, subjects with diabetes, those taking non-steroidal anti-inflammatory drugs, and those diagnosed with concomitant infection. We analyzed the data controlling for demographic variables, body mass index, use of contraceptives, had arthritis, and had gout. Among the 10,383 subjects, 2.3% had HCV and 16.7% had metabolic syndrome using the ATP III criteria. After controlling for the confounders, HCV was not associated with metabolic syndrome but associated with HOMA insulin resistance and inflammatory marker ferritin. Among subjects with both HCV and metabolic syndrome, the adjusted HOMA insulin level was higher than those without HCV and metabolic syndrome. In addition, the serum ferritin level was a strong predictor of HOMA insulin resistance. In clinical practice, serum ferritin can be obtained along with routine blood tests in any laboratory, and it has a potential to be a surrogate marker of insulin resistance in people with HCV and metabolic syndrome.
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PMID:Hepatitis C, metabolic syndrome, and inflammatory markers: results from the Third National Health and Nutrition Examination Survey [NHANES III]. 1691 55

There are limited data on nonalcoholic fatty liver disease (NAFLD) from India. The clinicopathological profile of Indian patients with NAFLD may be different from that of Western patients. One hundred NAFLD patients with increased liver enzymes were prospectively evaluated for clinical presentation, associated diseases, overweight/obesity, central obesity (n=54), presence of diabetes mellitus, lipid abnormalities, insulin resistance (n=39), metabolic syndrome (n=54), serum iron, serum ferritin, and transferrin saturation (n=60), and HFE gene mutations (n=30). Risk factors for the grade and stage of the disease on histology were studied in 38 biopsy-proven patients. Patients were treated with lifestyle modifications and ursodeoxycholic acid (UDCA). Seventeen nonresponder patients were treated with metformin. The majority of patients were males (n=70). Twenty percent of patients were overweight, 68% had obesity, and 78% had central obesity. Abnormal cholesterol, HDL, and triglycerides were present in 36%, 66%, and 53% of patients, respectively. Twelve percent of patients had diabetes mellitus and 16% patients had various associated diseases. All 22 (100%) patients studied by ITT and all but 1 (98%) studied by HOMA-IR were found to have reduced insulin sensitivity and 50% were found to have metabolic syndrome by the modified ATP III criteria. Two (3%) patients were found to have high serum iron, 4 (7%) patients had high ferritin, 5 (8%) patients had increased transferrin saturation, and 4 (13%) patients were found to be heterozygotes for H63D HFE gene mutation. Twenty patients of 38 (53%) had histological evidence of NASH (class 3=6, class 4=14). The other 18 (47%) qualified for class I (n=1) or class II (n=17) NAFLD. Four (10.5%) patients had bridging fibrosis and none had evidence of cirrhosis liver. Seventy-four (74%) patients achieved a biochemical response to lifestyle modification and UDCA. All 17 patients treated with metformin had a reduction in ALT level and 10 (59%) of them had normalization of their enzymes. We conclude that the clinicopathological profile of NAFLD in Indian patients is different from that in the West.
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PMID:The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. 1742 Sep 51

Mitochondria are involved in the development of organ failure in critical care diseases. However, the mechanisms underlying mitochondrial dysfunction are not clear yet. Inducible hemoxygenase (HO-1), a member of the heat shock protein family, is upregulated in critical care diseases and considered to confer cytoprotection against oxidative stress. However, one of the products of HO-1 is Fe2+ which multiplies the damaging potential of reactive oxygen species catalyzing Fenton reaction. The aim of this study was to clarify the relevance of free iron metabolism to the oxidative damage of the liver in endotoxic shock and its impact on mitochondrial function. Endotoxic shock in rats was induced by injection of lipopolysaccharide (LPS) at a dose of 8 mg/kg (i.v.). We observed that the pro-inflammatory cytokine TNF-alpha and the liver necrosis marker aspartate aminotransferase were increased in blood, confirming inflammatory response to LPS and damage to liver tissue, respectively. The levels of free iron in the liver were significantly increased at 4 and 8 h after onset of endotoxic shock, which did not coincide with the decrease of transferrin iron levels in the blood, but rather with expression of the inducible form of heme oxygenase (HO-1). The proteins important for sequestering free iron (ferritin) and the export of iron out of the cells (ferroportin) were downregulated facilitating the accumulation of free iron in cells. The temporarily increased concentration of free iron in the liver correlated with the temporary impairment of both mitochondrial function and tissue ATP levels. Addition of exogenous iron ions to mitochondria isolated from control animals resulted in an impairment of mitochondrial respiration similar to that observed in endotoxic shock in vivo. Our data suggest that free iron released by HO-1 causes mitochondrial dysfunction in pathological situations accompanied by endotoxic shock.
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PMID:A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction. 1798 71

Human RECQL4 protein was expressed in insect cells using a baculovirus protein expression system and it was purified to near homogeneity. The protein sedimented at a position between catalase (230 kDa) and ferritin (440 kDa) in glycerol gradient centrifugation, suggesting that it forms homo-multimers. Activity to displace annealed 17-mer oligonucleotide in the presence of ATP was co-sedimented with hRECQL4 protein. In ion-exchange chromatography, both DNA helicase activity and single-stranded DNA-dependent ATPase activity were co-eluted with hRECQL4 protein. The requirements of ATP and Mg for the helicase activity were different from those for the ATPase activity. The data suggest that the helicase migrates on single-stranded DNA in a 3'-5' direction. These results suggest that the hRECQL4 protein exhibits DNA helicase activity.
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PMID:DNA helicase activity in purified human RECQL4 protein. 1945 Nov 48

The myocardium is mainly composed of long-lived postmitotic cells with, if there is any at all, a very low rate of replacement through the division and differentiation of stem cells. As a consequence, cardiac myocytes gradually undergo pronounced age-related alterations which, furthermore, occur at a rate that inversely correlates with the longevity of species. Basically, these alterations represent the accumulation of structures that have been damaged by oxidation and that are useless and often harmful. These structures (so-called 'waste' materials), include defective mitochondria, aberrant cytosolic proteins, often in aggregated form, and lipofuscin, which is an intralysosomal undegradable polymeric substance. The accumulation of 'waste' reflects the insufficient capacity for autophagy of the lysosomal compartment, as well as the less than perfect functioning of proteasomes, calpains and other cellular digestive systems. Senescent mitochondria are usually enlarged, show reduced potential over their inner membrane, are deficient in ATP production, and often produce increased amounts of reactive oxygen species. The turnover of damaged cellular structures is hindered by an increased lipofuscin loading of the lysosomal compartment. This particularly restricts the autophagic turnover of enlarged, defective mitochondria, by diverting the flow of lysosomal hydrolases from autophagic vacuoles to lipofuscin-loaded lysosomes where the enzymes are lost, since lipofuscin is not degradable by lysosomal hydrolases. As a consequence, aged lipofuscin-rich cardiac myocytes become overloaded with damaged mitochondria, leading to increased oxidative stress, apoptotic cell death, and the gradual development of heart failure. Defective lysosomal function also underlies myocardial degeneration in various lysosomal storage diseases, while other forms of cardiomyopathies develop due to mitochondrial DNA mutations, resulting in an accumulation of abnormal mitochondria that are not properly eliminated by autophagy. The degradation of iron-saturated ferritin in lysosomes mediates myocardial injury in hemochromatosis, an acquired or hereditary disease associated with iron overload. Lysosomes then become sensitized to oxidative stress by the overload of low mass, redox-active iron that accumulates when iron-saturated ferritin is degraded following autophagy. Lysosomal destabilization is of importance in the induction and/or execution of programmed cell death (either classical apoptotic or autophagic), which is a common manifestation of myocardial aging and a variety of cardiac pathologies.
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PMID:The involvement of lysosomes in myocardial aging and disease. 1993 85

Honeybees (Apis mellifera) form superparamagnetic magnetite to act as a magnetoreceptor for magnetoreception. Biomineralization of superparamagnetic magnetite occurs in the iron deposition vesicles of trophocytes. Even though magnetite has been demonstrated, the mechanism of magnetite biomineralization is unknown. In this study, proteins in the iron granules and iron deposition vesicles of trophocytes were purified and identified by mass spectrometry. Antibodies against such proteins were produced. The major proteins include actin, myosin, ferritin 2, and ATP synthase. Immunolabeling and co-immunoprecipitation studies suggest that iron is stored in ferritin 2 for the purpose of forming 7.5-nm diameter iron particles and that actin-myosin-ferritin 2 may serve as a transporter system. This system, along with calcium and ATP, conveys the iron particles (ferritin) to the center of iron deposition vesicles for iron granules formation. These proteins and reactants are included in iron deposition vesicles during the formation of iron deposition vesicles from the fusion of smooth endoplasmic reticulum. A hypothetical model for magnetite biomineralization in iron deposition vesicles is proposed for honeybees.
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PMID:Identification and localization of proteins associated with biomineralization in the iron deposition vesicles of honeybees (Apis mellifera). 2154 30


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