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)

Infusion of rats with [U-14C]glycine resulted in labelling of glycine and serine in plasma albumin and liver ferritin. The patterms of labelling in these two proteins were not similar, suggesting that each is synthesized from a different pool of free amino acids.
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PMID:Compartmentation of albumin and ferritin synthesis in rat liver in vivo. 94

The domain organization of the zymogen subunits of the first component of human complement C1s, C1r2 and the complex C1s-C1r2-C1s was studied by electron microscopy. In the absence of Ca2+, monomeric C1s was visualized as a dumb-bell-shaped molecule consisting of two globular domains (center-to-center distance 11 nm) connected by a rod. One of the globular domains is assigned to the light chain (B-chain) of the activated molecule, which is homologous to trypsin and other serine proteases. The second globular domain and the rod are assigned to the heavy chain (A-chain) of CIs. The subunit C1r is a stable dimer in the presence or absence of Ca2+. This dimer C1r2 was visualized as composed of two dumb-bells of dimensions similar to those observed for C1s. These are connected near the junctions between the rod and one of the globular domains. This leads to the structure of an asymmetrical X with two inner closely spaced globules (center-to-center distance 7 nm) and two outer globules at a larger distance (14 nm). By comparison with fragment C1rII2, in which part of the A-chain is removed, the inner globular domains were assigned to the catalytic B-chains. This characteristic structure of C1r2 is readily recognized in the central portion of the thread-like 54 nm long C1s-C1r2-C1s complex formed in the presence of Ca2+. By affinity-labeling of C1s with biotin and visualization of avidin-ferritin conjugates in the reconstituted complex, it was demonstrated that C1s forms the outer portion of the complex. A detailed model of C1s-C1r2-C1s is proposed, according to which two C1s monomers bind to the outer globes of C1r2 by contacts between their heavy chains and those of C1r. According to this model the catalytic domains of C1r are located in the center and those of C1s at the very tips of the C1s-C1r2-C1s complex. On the basis of the structure of C1s-C1r2-C1s, we derived a detailed model of the C1 complex (composed of C1q and the tetrameric complex) and we discuss this model with a view to finding a possible activation mechanism of C1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional model of subcomponent C1 of human complement. 302 30

Expression of alpha 1 proteinase inhibitor (alpha 1-PI) in human mononuclear phagocytes may provide a local mechanism for inactivation of serine proteases at sites of tissue injury, thereby preventing incidental damage to surrounding tissue and allowing for orderly initiation of repair. We have previously shown that serine (neutrophilic or pancreatic) elastase and lipopolysaccharide (LPS) each mediate an increase in the expression of alpha 1-PI in human peripheral blood monocytes and bronchoalveolar macrophages. In this study we demonstrate that elastase and LPS have an additive positive regulatory effect on alpha 1-PI expression. Distinct pretranslational and translational mechanisms of action for elastase and LPS, respectively, account for the additive effect. The possibility that translational regulation of alpha 1-PI by LPS involves a mechanism analogous to that of the yeast gene GCN4 during amino acid starvation and that of the human ferritin gene in response to iron is discussed.
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PMID:Distinct and additive effects of elastase and endotoxin on expression of alpha 1 proteinase inhibitor in mononuclear phagocytes. 326 70

Three insect tissues have particular roles as filters to maintain the fluid composition of the hemolymph. Water and ions enter and leave through the midgut. The pericardial cells filter circulating hemolymph. Malpighian tubules, often with the rectum, allow resorption from a hemolymph filtrate that passes to the hindgut. All three tissues have plasma membrane infolds making a reticulum on their hemolymph surfaces, and all three have RER leading to SER extensions into their reticula. SER is a catch-all description for membranes lacking ribosomes in the pre-Golgi complex set of compartments of the vacuolar system. Some kinds of SER are well known for their role in housing enzymes for steroid metabolism and for detoxification. The SER ramifying within the plasma membrane reticular systems of tissues concerned with hemolymph filtration contains ferritin, suggesting that this SER has another, different function. In contrast to vertebrate cells, where ferritin is confined to the cytosol and lysosomes, we have found that in Calpodes and perhaps in most insects, ferritin occurs in the vacuolar system and not in the cytosol. Ferritin occurs naturally in the RER and SER of cells at the hind end of the midgut, in pericardial cells and in the yellow region of the Malpighian tubules. Additional ferritin is induced by loading the gut or hemolymph with iron. Overloading with iron causes ferritin secretion to the gut lumen. We propose that the SER in these cells functions in iron homeostasis by holding ferritin for loading and unloading as it moves to and from the reticulum at the cell surface where it can be maximally exposed to extracellular fluid flow.
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PMID:The induction and distribution of an insect ferritin--a new function for the endoplasmic reticulum. 651 41

Cell-specific differences occur in the primary structure of ferritin. For example, red cell and liver ferritin from bullfrog tadpoles differ by 1.5 times in serine content. To determine if cell-specific differences in ferritin primary structure are expressed in the tetraeicosomer, which thus might distinguish the proteins in a functional state, phosphorylation in vitro was employed as a probe using [gamma-32P]ATP and the catalytic subunit from the cAMP-dependent protein kinase of bovine skeletal muscle. Subunits of both proteins in the tetraeicosomers were phosphorylated. Based on tryptic peptide maps, five regions common to both red cell and liver apoferritin were phosphorylated, as confirmed for two peptides by amino acid analyses. [32P]Apoferritin from red cells yielded an additional four 32P-fragments by mapping, at least three of which were unique by amino acid analysis and, in one case, might represent a 32P-Fe complex bound by a fragment of the iron-binding site. One peptide appeared to be unique to liver apoferritin. High concentrations of ATP yielded one additional peptide common to liver and red cell and one red cell-specific peptide in the tryptic peptide maps. The maximum moles of 32P/molecule were 13 +/- 4 and 6 +/- 2, respectively, for red cell and liver apoferritin, which corresponded within experimental error to the number of 32P-tryptic peptides. The level of phosphorylation was, on the average, not more than one site/subunit. Furthermore, above certain levels of phosphorylation, some subunits in the assemblage of 24 appeared to be unavailable as substrates, possibly because of charge repulsion or conformational changes. The possibility that post-translational modifications of ferritin which amplify cell-specific structural features occur in vivo with cytoplasmic components, e.g. protein kinases, is considered in terms of the physiological availability of iron from different iron storage cells and developmental changes in iron storage.
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PMID:Cell-specific properties of red cell and liver ferritin from bullfrog tadpoles probed by phosphorylation in vitro. 660 21

Ferritin was trapped in negatively charged liposomes consisting of phosphatidyl choline and phosphatidyl serine in a molar ratio of 9:1. Unilamellar vesicles were prepared by ultrasonic treatment. HeLa cells were incubated with these liposomes for 2h and chased for 0, 2, 14 and 20 h. The migration pathway of ferritin in the cells was followed by quantitative electron microscopy. Ferritin was detected exclusively in cytosol and lysosomes. Evidence is presented that free ferritin in cytosol enters lysosomes.
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PMID:Autophagy of ferritin incorporated into the cytosol of Hela cells by liposomes. 735 75

The control of cellular iron homeostasis involves the coordinate post-transcriptional regulation of ferritin mRNA translation and transferring receptor mRNA stability. These regulatory events are mediated by a soluble cytoplasmic protein, iron regulatory factor (IRF), which binds specifically to mRNA hairpin structures, termed iron-responsive elements (IREs), in the respective mRNAs. IRF is modulated by variations of cellular iron levels and exists as either an apo-protein or a [4Fe-4S]-cluster protein. The two conformations show distinct, mutually exclusive functions. High-affinity IRE binding is observed with the apo-form induced by iron deprivation, but is lost under high iron conditions when IRF is converted to the [4Fe-4S]-cluster form which shows cytoplasmic aconitase activity. Moreover, IRE binding is inactivated by the sulfhydryl-oxidizing agent diamide and fully activated in vitro by 2% 2-mercapto-ethanol, whereas alkylation of IRF inhibits IRE binding. In the present study, we analyzed each of the above features using site-directed mutants of recombinant human IRF. The results support the bifunctional nature of IRF. We conclude that cysteines 437, 503 and 506 anchor the [4Fe-4S]-cluster, and are essential to the aconitase activity. Mutagenesis changing any of the cysteines to serine leads to constitutive RNA binding in 0.02% 2-mercaptoethanol. Cysteine 437 is particularly critical to the RNA-protein interaction. The spontaneous or diamide-induced formation of disulfide bonds between cysteines 437 and 503 or 437 and 506, in apo-IRF, as well as its alkylation by N-ethylmaleimide, inhibit binding to the IRE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutational analysis of the [4Fe-4S]-cluster converting iron regulatory factor from its RNA-binding form to cytoplasmic aconitase. 750 61

It is unclear whether running can affect iron stores. Results using the serum ferritin assay (SER FER) have been conflicting. Decreased red cell ferritin (RBC FER) values (< or = 4 ag/RBC) occur in iron depleted or inflammatory states. We compared the longitudinal changes of hemoglobin (Hb), SER FER, RBC FER, % saturation of total iron binding capacity (% sat TIBC), and daily dietary intake in 27 runners during a training program. These parameters were measured at days 0, 49 (range 48-52), and 115 (range 85-120). No significant changes occurred in the SER FER, % sat TIBC and Hb determinations throughout the study. Overall the RBC FER values trended down (mean values 11.7 ag/RBC to 7.7 ag/RBC; p = 0.06). Fifteen runners (56%) acquired RBC FER values in the iron deficient range (mean 6.8 ag/RBC to 2.4 ag/RBC; p < 0.05). These values differed significantly from the remaining 12 runners (mean 17.3 ag/RBC to 14.7 ag/RBC). The decline in RBC FER into the iron deficient range was primarily seen in a subset of runners who began with a RBC FER value < or = 10 ag/RBC (positive predictive value 0.79) and was independent of iron intake. We conclude that ferritin can be affected by running as recognized by the red cell ferritin assay. Moreover our results suggest that this decrease in red cell ferritin is likely a function of defective iron utilization rather than total body iron deficiency. A potential consideration is that this fall may occur as a result of repetitive running-associated injury and inflammation.
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PMID:The effect of running on serum and red cell ferritin. A longitudinal comparison. 755 22

The brain is the most compartmentalized organ. It is also highly aerobic. Because nerve cells grow but do not regenerate, the brain is the organ best suited for the accumulation of metabolic errors colocalized in specific areas of the brain over an extended period. Alzheimer's disease (AD) is primarily a neurological disorder of the elderly. It is suggested that this disorder results from the accumulation of such errors, and that AD onset aluminum and iron contribute to but do not necessarily initiate the onset of the disease. In vitro and in vivo evidence summarized here suggests that this is effected by interfering in the utilization of glucose and glucose-6-phosphate, and sequestration of iron by ferritin. beta-amyloid precusor proteins (beta-APPs) are normal components of the human brain and some other tissues. Proteolysis of these, presumably by serine proteases, generates a 39 to 42 amino acid long peptide, the alpha-amyloid (beta-AP). In AD brains, beta-AP aggregates into plaque, the hallmark of AD brains. Some of the alpha-APPs also contain a 56 amino acid long segment which inhibits serine proteases. We show that in vitro, at pH 6.5, aluminum activates beta-chymotrypsin 2-fold and makes it dramatically resistant to protease inhibitors such as bovine pancreatic trypsin inhibitor (bPTI) or its mimic present in the beta-amyloid precursor proteins (beta-APPs). Iron and oxygen are reported to favor cross-linking of beta-AP in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iron and aluminum homeostasis in neural disorders. 784 99

IgG autoantibodies against malondialdehyde-modified LDL (alpha oxLDL), antiphospholipid antibodies (APA) and oxidation- and lipoprotein-related analytes were assayed in sera from healthy subjects (51 males, 115 females, aged 22-63 years). alpha OxLDL levels were associated (P < 0.03) with IgG alpha cardiolipin (r = 0.18), IgM alpha cardiolipin (r = 0.17) and IgM alpha phosphatidyl-serine (r = 0.16) but not with age, cholesterol, triglyceride, apolipoproteins B and AI, lipoprotein(a), lipid peroxides, ceruloplasmin, copper, ferritin, transferrin or iron. APA levels were inversely associated with levels of both oxidation- and lipoprotein-related analytes. Ferritin (3.5%) and alpha oxLDL (1.4%) contributed independently to variation in IgG alpha cardiolipin levels, and apo B (2%) to variation in IgM alpha cardiolipin levels. These associations are small, indicating that there are no major biological associations between the measured variables. The lack of association between alpha oxLDL and lipoprotein- or oxidation-related analytes suggests that the relevant antigen is not in serum.
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PMID:Anti-oxidized LDL antibodies and antiphospholipid antibodies in healthy subjects: relationship with lipoprotein- and oxidation-related analytes. 857 26


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