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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ubiquitin-protein conjugates in the hippocampus were analyzed by immunoblotting with a monoclonal anti-ubiquitin antibody. In the CA1 region, Triton X-100 insoluble ubiquitin-protein conjugates increased after 24 hr following 20 min of ischemia. When the total hippocampi were fractionated subcellularly, ubiquitin-protein conjugates increased in the particulate, especially in the mitochondrial fraction. The ubiquitin-protein conjugates were solubilized by SDS, or were partially solubilized by urea. The results indicate that insoluble ubiquitin-protein conjugates increase after ischemia.
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PMID:Subcellular distribution of ubiquitin-protein conjugates in the hippocampus following transient ischemia. 132 64

Ubiquitin is involved in the degradation of denatured proteins in the recovery process after various stresses. To clarify the different responses of the ubiquitin system in the hippocampal neurons after ischemia, we chose 7.5 min of sublethal forebrain ischemia in the rat. After 7.5 min of ischemia, ubiquitin-like immunoreactivity (UIR) in most of the hippocampal pyramidal cells, except for the interneurons, diminished after 3 h of reperfusion, but enhanced UIR and subsequent recovery of UIR were observed in the different hippocampal regions after 24 h of reperfusion. The most prolonged recovery of UIR in the hippocampal cells was observed in the CA1 neurons after 72 h of reperfusion. Immunoblot analysis of the proteins extracted from CA1 region showed that high-mol-wt ubiquitin conjugates (HMWUC) above 40 kDa increased, whereas free ubiquitin and ubiquitinated histone 2A decreased slightly after 4 h and 24 h of reperfusion. At 72 h of reperfusion, HMWUC decreased to the original level and free ubiquitin slightly increased beyond the control level. These results suggested that (1) diminished UIR does not always mean depletion of entire ubiquitin-protein conjugates; (2) even after sublethal ischemia, damaged proteins in the CA1 neurons may increase, and it may take a long time for elimination of these proteins.
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PMID:Changes in ubiquitin and ubiquitin-protein conjugates in the CA1 neurons after transient sublethal ischemia. 166 59

Ubiquitin has previously been identified as a component of neuronal inclusions in neurodegenerative disorders. In this investigation, we examined tissue from cases of Alzheimer's disease (AD), Pick's disease, Parkinson's disease (PD), and progressive supranuclear palsy (PSP) to identify previously unrecognized ubiquitinated structures and to assess the evolution of neuronal inclusions. In AD, approximately 60% of neurofibrillary tangles (NFTs) that were stained with an anti-paired helical filaments (PHF) serum were identified by the ubiquitin antibodies. Extracellular NFTs were not labelled with anti-PHF but were unlabelled or weakly labelled with anti-ubiquitin antibodies. In Pick's disease, most Pick bodies were strongly labelled by the ubiquitin antibodies, and in addition some hippocampal CA1 neurones contained granular or strand-like ubiquitin-immunoreactive (IR) inclusions associated with more typical Pick bodies. Typical Lewy bodies in PD cases showed an unlabelled central core with an outer ring intensely labelled by ubiquitin antibodies. Pale bodies in pigmented substantia nigra neurones appeared as large well-defined, rounded structures without an identifiable core or peripheral zone. Some pale bodies were unlabelled by ubiquitin antibodies, but others showed labelling of variable intensity. Pale bodies which were labelled by ubiquitin antibodies tended also to be labelled by BF10, a monoclonal antibody against phosphorylated neurofilaments. We suggest that pale bodies in PD may represent stages in the formation of Lewy bodies. In addition, we observed numerous spindle-shaped ubiquitin-IR swellings of dendrites of pigmented substantia nigra neurones. In contrast to inclusions of AD and Pick's disease, the PHF-positive fibrillary neuronal inclusions of PSP were either unlabelled or only weakly labelled by ubiquitin antibodies. No ubiquitinated structures were seen in neurones from corresponding areas in aged controls. Identification of ubiquitinated proteins in neurodegenerative disorders may provide insights into molecular events associated with cell death.
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PMID:New aspects of the pathology of neurodegenerative disorders as revealed by ubiquitin antibodies. 255 99

Using immunohistochemistry, we visualized the localization of ubiquitin in the gerbil hippocampus following 3 min of ischemia with or without pretreatment with 2 min of sublethal ischemia and 3 days of reperfusion. Ubiquitin immunoreactivity in the hippocampus disappeared 4 h after 3 min of ischemia both with and without pretreatment. The immunoreactivity in the CA3 and the dentate gyrus recovered by 24 h, but never recovered in the CA1, where delayed neuronal death takes place, without pretreatment. However, the pretreatment, which protects against CA1 neuronal damage, led to recovery of ubiquitin immunoreactivity in the CA1 by 48 h. Thus, recovery of ubiquitin may be a prerequisite to neuronal survival after ischemia and the role of ubiquitin in ischemic tolerance was suggested.
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PMID:Immunohistochemical localization of ubiquitin in gerbil hippocampus with induced tolerance to ischemia. 839 55

Ubiquitin gene expression following transient forebrain ischemia in the rat was analyzed by three probes which were specific for UbC, UbB and UbS30 mRNA. According to the in situ hybridization studies, each type of ubiquitin gene expression decreased at 30 min of reperfusion following 20 min of forebrain ischemia, thereafter increased, and then reached a peak at 4-6 h, both in the cortex and hippocampus. These changes returned to the control level after 24-48 h of recirculation. Among the three ubiquitin transcripts, changes in UbC expression were more marked in the hippocampus, and persistent expression of UbC transcripts in the CA1 and CA3 regions was observed at 24 h of reperfusion. With dot-blot analysis, significant increases in the UbC transcripts were noted at 4 h of reperfusion in the hippocampus, and at 6 h in the cortex following 20 min of ischemia. These results suggest that changes in UbC expression might be a good indicator of ischemic stress.
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PMID:Ubiquitin gene expression following transient forebrain ischemia. 896 46

Ubiquitin (Ub) is a small 76-residue protein, involved in intracellular protein degradation through a specific ATP-dependent system, which uses Ub as a tag to label proteins committed to be hydrolyzed by a specific 26 S protease. PGP-9.5 is another important component of the Ub system, i.e. a neuron-specific carboxyl-terminal hydrolase, which recycles Ub from Ub-polypeptide complexes. We have investigated the expression of Ub and PGP-9.5 in rat hippocampal neurons in an early phase of reperfusion in a model of transient global brain ischemia/hypoxia (bilateral occlusion of common carotid arteries for 10 min accompanied by mild hypoxia-15% O2-for 20 min), by means of immunohistochemical methods using light and electron microscopy. The intensity of Ub and PGP-9.5 immunoreactivity was evaluated by image analysis. We have detected a marked increase of Ub immunoreactivity (UIR) in neurons of CA1, CA2, CA3, CA4, and dentate gyrus subfields 1 hr after ischemia/hypoxia (but not after hypoxia only), statistically significant as confirmed by image analysis. Such increase in immunoreactivity in ischemic/hypoxic rats was localized essentially in the nuclei of hippocampal neurons. There were no changes in PGP-9.5 immunoreactivity. The data suggest that in the present model of rat brain ischemia/hypoxia Ub is involved in the neuronal stress response.
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PMID:Ubiquitin-mediated stress response in a rat model of brain transient ischemia/hypoxia. 902 69

Using in situ hybridization techniques with an RNA probe coding for approximately 3.5 repeats of ubiquitin, corresponding to the polyubiquitin genes, we were able to demonstrate that under normal conditions the expression of the ubiquitin genes predominates specially in regions CA1, CA2 and CA3 of the hippocampus, in the dentate gyrus and in Purkinje cells of the cerebellum, being less prominent in neuronal cell bodies of the cerebral cortex. When the animals were submitted to an acute oxidative stress by injection of Fe/Dextran, the hybridization signal was apparently increased in the above mentioned regions of the hippocampus and in the cerebral cortex. On the other hand, the animals chronically injected with Fe/Dextran showed a highly intense gene expression in the cerebral cortex and in the cerebellum, particularly in the granular cell layer of this structure. The hybridization signal of the transcripts was absent in the Purkinje cells. The results suggest that the expression of the ubiquitin genes by CNS neurons depends on the anatomical location of the cells and that it increases as a consequence of the oxidative stress conditions to which they are submitted.
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PMID:Expression of the ubiquitin genes in brain of normal and Fe/Dextran injected rats. 913 Feb 43

A 76-year-old woman with olivopontocerebellar atrophy (OPCA) presented with progressive intellectual deterioration. She showed cerebellar ataxia and muscle atrophy and weakness, and gradually developed generalized dementia with visuospatial disturbance. An autopsy revealed numerous senile plaques (SPs), neurofibrillary tangles (NFTs) and neuropil threads particularly in the CA1, subiculum and entorhinal cortex and to a lesser degree in the cerebral neocortex shown by immunostaining and specific silver impregnation techniques. The nucleus basalis of Meynert had numerous NFTs with fibrillary gliosis and neuronal cell loss. The basis pontis was markedly atrophied and the pontine nucleus had severe neuronal depopulation and gliosis. The pontine transverse fibers were demyelinated with their axons being fragmented. The cerebellar white matter was also severely degenerated. The striatum, Onuf's and intermediolateral nuclei of the spinal cord remained unchanged. Ubiquitin immunohistochemistry and Gallyas silver impregnation technique revealed oligodendroglial inclusions in the pontine nucleus, corticopontine tract, cerebral and cerebellar white matter. On double immunostaining of KP1 and ubiquitin, globular neurite SPs encircled by KP1-positive fibrous structures were found in the hippocampus and cerebral neocortex. The curly neurite SPs contained KP1-positive granules. The KP1-positive microglial cells were distributed widely in the cerebral white matter and HLA-DR-positive ones were found around the SPs. The present case showed generalized dementia compatible with Alzheimer's disease (AD) and had a pathologically limbic type of late onset AD. This is the first case where AD affected non-familial OPCA.
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PMID:Non-familial olivopontocerebellar atrophy combined with late onset Alzheimer's disease: a clinico-pathological case report. 984 5

Electrospray ionization-Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry allows for high-resolution, accurate mass analysis of multiply charged ions of proteins. In the work described here, the ability of ESI-FTICR to distinguish small differences in molecular mass is evaluated. Ubiquitin was used as an internal mass calibration standard to measure the molecular mass of cytochrome c, myoglobin, and several carbonic anhydrase isoforms. Mass calibration was based on the tallest isotopic peak of each ubiquitin charge state. Ubiquitin performed well as an internal standard because its charge states covered the appropriate mass range, interference was minimal, and the tallest peak was easily identified. The peak masses of cytochrome c (12.5 kDa) and myoglobin (17 kDa) were measured to an accuracy of about 0.02 Da (<2ppm). However, errors of 1.0 Da were observed for some individual determinations because of the difficulty in identifying the tallest peak. When the technique was applied to bovine carbonic anhydrase II, even combining data from several charge states did not yield an unequivocal assignment of the tallest peak, resulting in a mass assignment of 29,023.7 or 29,024.7. Similarly, measurements of two isoforms with a mass difference of 1 Da, human carbonic anhydrase I, pI 6.0 and 6.6, yielded overlapping values for the mass of the tallest peak. However, these two isoforms were clearly distinguished by (a) identification of the tallest peak using a measurement of average mass as a guide and (b) comparison of the isotopic peak intensity patterns.
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PMID:Distinguishing small molecular mass differences of proteins by mass spectrometry. 965 79

Ubiquitin, an essential protein in nonlysosomal proteolytic system, is expressed after metabolic stress to the cell. The authors investigated stress response of ubiquitin in the hippocampus of the Mongolian gerbil after forebrain ischemia. The level of hippocampal ubiquitin was compared with that under ischemic tolerance induced by ischemic preconditioning. The authors also studied ubiquitin gene expression using in situ hybridization method. Transient ischemia resulted in consumption of free ubiquitin and an increase of multiubiquitin chains. These changes were transient in the hippocampus outside of the CA1 region where neurons survived, whereas it was persistent in the CA1 region where neurons were destined to die after ischemia. Under tolerant condition, subsequent ischemia provoked rapid recovery and further increase of free ubiquitin. The signal of ubiquitin messenger ribonucleic acid was continuously detected after ischemia, not only under tolerant conditions, but without tolerance induced by preconditioning. Thus, ubiquitin stress response takes place, at least at a transcriptional level, in dying CA1 neurons. Under tolerant conditions, however, subsequent ischemia in the CA1 region induces the stress response of ubiquitin up to the translational level, leading to the rapid restoration of protein synthesis and to eventual neuronal survival.
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PMID:Ubiquitin stress response in postischemic hippocampal neurons under nontolerant and tolerant conditions. 1041 29


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