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)

Small cell lung cancer (SCLC) is one of the most malignant tumors, especially often associated with nonmetastatic neurological disorders, corresponding to paraneoplastic neurological syndromes. The pathogenesis of which is unknown, however, mostly attributed to autoimmune processes. The aim of the study was to determine the pattern of the peripheral nervous system damage in SCLC. To provide further data contributing to the pathomechanism underlying these syndromes, immunocytochemical studies were initiated. Autopsy material was collected from 47 cases of SCLC. All these patients were examined clinically. The sections from the cervical, thoracic and lumbosacral segments of the spinal cord with spinal roots and dorsal root ganglia were taken. For immunohistochemistry following antisera were used: GFAP, MBP, IgG, IgM, ferritin, ubiquitin, alpha 1-antichymotrypsin, alpha 2-macroglobulin, C3 and C5b9 complement fractions. In 18 patients peripheral nervous system disturbances were diagnosed neurologically, 21 of cases presented neuromuscular disorders by emg. Among the nonmetastatic lesions most often a damage of dorsal root ganglia was observed (in 33 cases). Degeneration of the spinal roots was absent only in 8 cases. In 21 cases degenerative changes of motor neurons within anterior horn were present. In no case ubiquitin-positive inclusion bodies within the motor neurons could be found. In 8 cases extravasation of the IgG with diffuse labeling of the grey matter was observed. IgM immunoreactivity was markedly less frequently present, C5b9 complement fraction immunoreactivity was also confined only to cases with peripheral nervous system disturbances. Therefore, our preliminary data seem to confirm the participation of humoral immunity in paraneoplastic syndrome pathogenesis.
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PMID:Peripheral nervous system alterations in small cell lung cancer. Clinico-pathological study. 133 75

The cerebellum, frontal cortex, hippocampal and parahippocampal regions of 100 patients older than 80 years, most of whom had died of stroke, were examined. Eighteen percent were diagnosed as clinically demented. On the specimens labeled previously with Thioflavin S and Bielschowsky method, immunohistochemical studies were performed with Fab (antigen-binding fragment) of the anti beta-amyloid antibody 4G8. Positive amyloid immunoreactivity was observed in the cerebrum in 71 of 100 cases, Cerebella of 31 subjects of 71 with cerebral amyloidosis also revealed amyloid deposits. They appeared in various morphological forms, such as diffuse plaques and focal subpial deposits, as well as classical and primitive neuritic plaques. Cases with amyloid in the cerebellum alone were not observed. Beta-amyloid deposits in the cerebellum were associated with a significant number of beta-amyloid plaques in the cerebrum, which showed other Alzheimer-type pathology, also in individuals without clinical symptoms of dementia. There was no correlation either between cerebellar amyloid deposits and clinical cerebellar symptoms or between the presence of diabetes mellitus, arterial hypertension, and neuropathological changes. A clear association of microglial cells with amyloid deposits in the cerebellum was demonstrated. In our experience, LN-1 and RCA-1 were not as suitable for formalin-fixed paraffin-embedded tissue, as was anti-ferritin. Negative staining for tau-1 and positive staining for anti-ubiquitin characterized neurites within primitive and classical plaques. No neurofibrillary pathology was detected in the cytoplasm of cerebellar neurons when we used anti tau-1 labeling.
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PMID:beta-Amyloid deposits within the cerebellum of persons older than 80 years of age. 134 Sep 21

The expression of the genes for serum albumin and several other plasma proteins is decreased in animals consuming inadequate amounts of dietary protein. To define the specificity of this phenomenon, we examined the effect of dietary protein restriction on the abundance of the mRNA for nine genes in rat liver. The results of this and previous studies indicate that genes in liver can be divided into two classes based on their response to protein restriction. Group I genes (albumin, transthyretin, carbamyl phosphate synthetase-I, class I alcohol dehydrogenase, insulin-like growth factor-I) exhibit decreased expression in response to protein restriction. In contrast, the expression of group II genes (hypoxanthine-guanine phosphoribosyl transferase, ubiquitin, H-ferritin, insulin-like growth factor binding proteins-1, -2 and -4) is either unchanged or increased in response to protein restriction. To investigate the molecular mechanism(s) leading to the decreased level of albumin and transthyretin mRNA in protein-restricted animals, the effect of protein restriction on the abundance of albumin and transthyretin nuclear transcripts was examined. The results demonstrated that protein restriction specifically decreased the abundance of albumin and transthyretin nuclear transcripts, indicating that the reduction in mRNA levels is caused at least partly by a decrease in gene transcription.
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PMID:Protein restriction specifically decreases the abundance of serum albumin and transthyretin nuclear transcripts in rat liver. 802 54

We showed previously that the abundance of serum albumin mRNA is decreased in H4-II-E rat hepatoma cells limited for a single essential amino acid (phenylalanine, methionine, leucine, or tryptophan). To define the specificity of this phenomenon, we examined the effect of amino acid limitation on the abundance of mRNAs for 19 genes in the H4-II-E cells. These genes included six genes whose expression is either completely liver-specific or highly enriched in the liver compared with other tissues [albumin, transthyretin (TTR), transferrin, carbamyl phosphate synthetase-I, urate oxidase, class I alcohol dehydrogenase], as well as a number of ubiquitously expressed "housekeeping" genes. The results indicated that the 19 genes could be divided into three classes based on their response to amino acid limitation. Class I genes (the six liver-specific genes and alpha-tubulin) exhibit decreased expression in response to amino acid limitation. The expression of class II genes [beta 2-microglobulin, hypoxanthine-guanine phosphoribosyl transferase (HPRT), H-ferritin, ubiquitin (UbB), insulin-like growth factor binding protein-4, HNF-1 alpha] is not significantly affected by amino acid limitation. Class III genes [gadd153, beta-actin, ubiquitin (UbC), phosphoglycerate kinase-1, C/EBP alpha, C/EBP beta] exhibit increased expression in response to amino acid limitation. Thus, specific inductive as well as repressive effects on gene expression are quite common in amino acid-limited cells. The observation that all six genes whose expression is liver-specific exhibited decreased expression in amino acid-limited cells suggests a common mode of regulation of these genes by amino acid availability. The strong induction by amino acid limitation of the C/EBP inhibitor gadd153 is of interest in this regard, as increased levels of gadd153 could interfere with C/EBP, which is required for high expression of most liver-specific genes. To investigate further the molecular mechanism for the decrease in albumin mRNA abundance, albumin nuclear transcript levels were quantified in control and tryptophan-limited cells. Tryptophan limitation caused a decrease in albumin nuclear transcript abundance, and this decrease preceded the decrease in albumin mRNA, suggesting that the decrease in albumin mRNA was caused at least partly by a decrease in albumin gene transcription. Additional experiments with actinomycin D indicated that albumin mRNA was also destabilized in the tryptophan-limited cells. Thus, the overall results indicate that the decrease in albumin mRNA in the tryptophan-limited cells is caused by a specific decrease in albumin nuclear transcript abundance and destabilization of albumin mRNA.
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PMID:Effect of amino acid limitation on the expression of 19 genes in rat hepatoma cells. 818 73

Studies employing a bank of antisera applied to sections of LR White embedded AD and normal ageing brain tissue, may throw new light on the derivation of CA. Conspicuous levels of immunoreactivity were found in the CA of both tissues with markers for oligodendrocytic proteins such as antisera against myelin basic proteolipid protein, galactocerebroside and myelin/oligodendrocyte glycoprotein. CA were unreactive with MRC OX-42, a marker for microglia and macrophages. In a previous publication we demonstrated that the much more abundant CA in the brains of Alzheimer's disease (AD) sufferers, although slightly more varied in their immunoreactivity than those found in normally ageing controls, were universally immunoreactive with anti-tau, a neuronally derived protein and often also contained amyloid. The cores of CA were not immunoreactive with anti-GFAP, suggesting a lack of involvement with astrocytes. Our results now show that in addition to amyloid and neuronal proteins, a significant proportion of the content of CA is derived from oligodendrocytes and/or myelin. The substantial Fe peak previously reported following X-ray microanalysis of CA was probably due to ferritin. However, immunostaining with antisera to ferritin showed that high ferritin immunoreactivity was common to both micro- and macroglia as well as CA. More significantly, the immunoreactivity of CA with anti-ubiquitin suggests that degeneration of neuronal/oligodendrocytic elements may precede CA formation.
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PMID:New immunocytochemical evidence for a neuronal/oligodendroglial origin for corpora amylacea. 820 42

Oxidatively modified ferritin is selectively recognized and degraded by the 20S proteasome. Concentrations of hydrogen peroxide (H2O2) higher than 10 micromol/mg of protein are able to prevent proteolytic degradation. Exposure of the protease to high amounts of oxidants (H2O2, peroxynitrite and hypochlorite) inhibits the enzymic activity of the 20S proteasome towards the fluorogenic peptide succinyl-leucine-leucine-valine-tyrosine-methylcoumarylamide (Suc-LLVY-MCA), as well as the proteolytic degradation of normal and oxidant-treated ferritin. Fifty per cent inhibition of the degradation of the protein substrates was achieved using 40 micromol of H2O2/mg of proteasome. No change in the composition of the enzyme was revealed by electrophoretic analysis up to concentrations of 120 micromol of H2O2/mg of proteasome. In further experiments, it was found that the 26S proteasome, the ATP- and ubiquitin-dependent form of the proteasomal system, is much more susceptible to oxidative stress. Whereas degradation of the fluorogenic peptide, Suc-LLVY-MCA, by the 20S proteasome was inhibited by 50% with 12 micromol of H2O2/mg, 3 micromol of H2O2/mg was enough to inhibit ATP-stimulated degradation by the 26S proteasome by 50%. This loss in activity could be followed by the loss of band intensity in the non-denaturing gel. Therefore we concluded that the 20S proteasome was more resistant to oxidative stress than the ATP- and ubiquitin-dependent 26S proteasome. Furthermore, we investigated the activity of both proteases in K562 cells after H2O2 treatment. Lysates from K562 cells are able to degrade oxidized ferritin at a higher rate than non-oxidized ferritin, in an ATP-independent manner. This effect could be followed even after treatment of the cells with H2O2 up to a concentration of 2mM. The lactacystin-sensitive ATP-stimulated degradation of the fluorogenic peptide Suc-LLVY-MCA declined, after treatment of the cells with 1mM H2O2, to the same level as that obtained without ATP stimulation. Therefore, we conclude that the regulation of the 20S proteasome by various regulators takes place during oxidative stress. This provides further evidence for the role of the 20S proteasome in the secondary antioxidative defences of mammalian cells.
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PMID:Comparative resistance of the 20S and 26S proteasome to oxidative stress. 979 5

Crystallization trials using three polyoxyethylene surfactants as precipitating agents are described. Of the eight soluble proteins screened, five were successfully crystallized at the first attempt. These included lysozyme, catalase, ferritin, ribonuclease A and ubiquitin. Further work suggested that these surfactants could also be suitable for cryo-crystallographic analysis of crystals. At the concentrations used in the crystallization trials [10-40%(v/v)], they are capable of promoting the formation of non-crystalline glasses at cryogenic temperatures (77K). This would facilitate crystal mounting and allow the minimization of crystal irradiation damage. Results from this study also suggest that proteins remain stable at high concentrations of these surfactants [40%(w/v)] and over long time periods (>1 month). A number of membrane proteins were also screened for crystallization. These included photosystems I and II and light harvesting complexes I and II from spinach and bacteriorhodopsin from Halobacterium halobium++. The trial s were unsuccessful both in the absence and presence of heptane-1,2,3-triol and over a wide range of surfactant concentrations.
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PMID:A novel approach for the crystallization of soluble proteins using non-ionic surfactants. 986 32

In mammalian cells, regulation of the expression of proteins involved in iron metabolism is achieved through interactions of iron-sensing proteins known as iron regulatory proteins (IRPs), with transcripts that contain RNA stem-loop structures referred to as iron responsive elements (IREs). Two distinct but highly homologous proteins, IRP1 and IRP2, bind IREs with high affinity when cells are depleted of iron, inhibiting translation of some transcripts, such as ferritin, or turnover of others, such as the transferrin receptor (TFRC). IRPs sense cytosolic iron levels and modify expression of proteins involved in iron uptake, export and sequestration according to the needs of individual cells. Here we generate mice with a targeted disruption of the gene encoding Irp2 (Ireb2). These mutant mice misregulate iron metabolism in the intestinal mucosa and the central nervous system. In adulthood, Ireb2(-/-) mice develop a movement disorder characterized by ataxia, bradykinesia and tremor. Significant accumulations of iron in white matter tracts and nuclei throughout the brain precede the onset of neurodegeneration and movement disorder symptoms by many months. Ferric iron accumulates in the cytosol of neurons and oligodendrocytes in distinctive regions of the brain. Abnormal accumulations of ferritin colocalize with iron accumulations in populations of neurons that degenerate, and iron-laden oligodendrocytes accumulate ubiquitin-positive inclusions. Thus, misregulation of iron metabolism leads to neurodegenerative disease in Ireb2(-/-) mice and may contribute to the pathogenesis of comparable human neurodegenerative diseases.
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PMID:Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. 1117 92

We used particle bombardment to produce transgenic wheat and rice plants expressing recombinant soybean ferritin, a protein that can store large amounts of iron. The cDNA sequence was isolated from soybean by RT-PCR and expressed using the constitutive maize ubiquitin-1 promoter. The presence of ferritin mRNA and protein was confirmed in the vegetative tissues and seeds of transgenic wheat and rice plants by northern and western blot analysis, respectively. The levels of ferritin mRNA were similar in the vegetative tissues of both species, but ferritin protein levels were higher in rice. Both ferritin mRNA and protein levels were lower in wheat and rice seeds. ICAP spectrometry showed that iron levels increased only in vegetative tissues of transgenic plants, and not in the seeds. These data indicate that recombinant ferritin expression under the control of the maize ubiquitin promoter significantly increases iron levels in vegetative tissues, but that the levels of recombinant ferritin in seeds are not sufficient to increase iron levels significantly over those in the seeds of non-transgenic plants.
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PMID:Constitutive expression of soybean ferritin cDNA in transgenic wheat and rice results in increased iron levels in vegetative tissues but not in seeds. 1120 73

Oxidatively modified proteins that accumulate in aging and many diseases can form large aggregates because of covalent cross-linking or increased surface hydrophobicity. Unless repaired or removed from cells, these oxidized proteins are often toxic, and threaten cell viability. Most oxidatively damaged proteins appear to undergo selective proteolysis, primarily by the proteasome. Previous work from our laboratory has shown that purified 20 S proteasome degrades oxidized proteins without ATP or ubiquitin in vitro, but there have been no studies to test this mechanism in vivo. The aim of this study was to determine whether ubiquitin conjugation is necessary for the degradation of oxidized proteins in intact cells. We now show that cells with compromised ubiquitin-conjugating activity still preferentially degrade oxidized intracellular proteins, at near normal rates, and this degradation is still inhibited by proteasome inhibitors. We also show that progressive oxidation of proteins such as lysozyme and ferritin does not increase their ubiquitinylation, yet the oxidized forms of both proteins are preferentially degraded by proteasome. Furthermore, rates of oxidized protein degradation by cell lysates are not significantly altered by addition of ATP, excluding the possibility of an energy requirement for this pathway. Contrary to earlier popular belief that most proteasomal degradation is conducted by the 26 S proteasome with ubiquitinylated substrates, our work suggests that oxidized proteins are degraded without ubiquitin conjugation (or ATP hydrolysis) possibly by the 20 S proteasome, or the immunoproteasome, or both.
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PMID:Ubiquitin conjugation is not required for the degradation of oxidized proteins by proteasome. 1240 7


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