Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patterns of expression of the bcl-2, bax, and bci-X genes were examined immunohistochemically in neurons of the adult rat brain before and after 10 min of global ischemia induced by transient cardiac arrest. High levels of the cell death promoting protein Bax and concomitant low levels of the apoptosis-blocking protein Bcl-2 were found in some populations of neurons that are particularly sensitive to cell death induced by transient global ischemia, such as the CA1 sector of the hippocampus and the Purkinje cells of the cerebellum. Moreover, within 0.5 to 3 hr after an ischemic episode, immunostaining for Bax was markedly increased within neurons with morphological features of degeneration in many regions of the brain. Use of a two-color staining method for simultaneous analysis of Bax protein and in situ detection of DNA-strand breaks revealed high levels of Bax immunoreactivity in many neurons undergoing apoptosis. Postischemic elevations in Bax protein levels in the hippocampus, cortex, and cerebellum were also demonstrated by immunoblotting. At early times after transient ischemia, regulation of Bcl-2 and Bcl-x protein levels varied among neuronal subpopulations, but from 3 hr on, those neurons with morphological evidence of degeneration uniformly contained reduced levels of Bci-2 and particularly Bci-X immunoreactivity. The findings suggest that differential expression of some members of the bcl-2 gene family may play an important role in determining the relative sensitivity of neuronal subpopulations to ischemia and that postischemic alterations in the expression of bax, bcl-2, and bcl-x may contribute to the delayed neuronal cell death that occurs during the repurfusion phase after a transient ischemic episode.
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PMID:Upregulation of bax protein levels in neurons following cerebral ischemia. 747 1

Bcl-2 protein has been suggested to be one of the proteins preventing apoptosis in a variety of cell types. Recently, apoptosis has been suggested to have an important role in the pathogenesis of Alzheimer's disease (AD). We have utilized Bcl-2 immunohistochemical methods to examine Bcl-2 in the hippocampus and entorhinal cortex of AD patients ranging in clinical and neuropathological severity from mild to severe and compared these results to those obtained from age-matched controls. Immunoreactivity for Bcl-2 was predominantly found within neurons. Bcl-2 immunostaining within AD tissue was increased relative to controls in most neurons of the entorhinal cortex, subiculum, CA1, CA2, CA3, hilus and dentate gyrus. Relative Bcl-2 staining increased in parallel with increasing disease severity. However, neurons exhibiting immunoreactivity for markers of neurofibrillary tangle formation (AT8 and PHF-1) showed reduced Bcl-2 staining, suggesting that Bcl-2 may be down regulated in these degenerating neurons. Bcl-2 immunoreactivity within astrocytes and the vasculature was also increased in AD. These results suggest that Bcl-2 protein may have a role in compensation responses to AD pathology, perhaps affording to the remaining neurons a margin of protection from apoptosis.
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PMID:Immunoreactivity for Bcl-2 protein within neurons in the Alzheimer's disease brain increases with disease severity. 859 92

The observation that delayed death of CA1 neurons after global ischemia is inhibited by protein synthesis inhibitors suggests that the delayed death of these neurons is an active process that requires new gene expression. Delayed death in CA1 has some of the characteristics of apoptotic death; however, candidate proapoptotic proteins have not been identified in the CA1 after ischemia. We studied the expression of Bax protein and mRNA, a member of the bcl-2 family that is an effector of apoptotic cell death, after global ischemia in the four-vessel global ischemia model in the rat and compared these results with the expression of the antiapoptotic gene bcl-2. Bax mRNA and protein are both expressed in CA1 before delayed death, whereas bcl-2 protein is not expressed. Bcl-2 protein expression, but not that of Bax, is increased in CA3, a region that is ischemic but less susceptible to ischemic injury. In the dentate gyrus, both Bax and bcl-2 proteins are expressed. The selective expression of Bax in Ca1 supports the hypothesis that Bax could contribute to delayed neuronal death in these vulnerable neurons by an independent mechanism or by forming heterodimers with gene family members other than bcl-2.
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PMID:Expression of the apoptosis-effector gene, Bax, is up-regulated in vulnerable hippocampal CA1 neurons following global ischemia. 866 27

Time-course expression of Bax and Bcl-2 proteins, identified as apoptosis-regulating molecules, was assessed in gerbil hippocampus following transient forebrain ischemia. Brain sections from animals sacrificed at 48, 72, 96 h and 7 days following 5 min ischemia were immunohistochemically evaluated using polyclonal antibodies specific for Bax and Bcl-2 proteins, respectively. The intensity of Bax expression in CA1 neurons increased with time and peaked at 72 h, and immediately disappeared at 96 h following 5 min ischemia. No expression of Bcl-2 in the CA1 neurons was recognized in all the time evaluated.
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PMID:Immunohistochemical detection of Bax and Bcl-2 proteins in gerbil hippocampus following transient forebrain ischemia. 868 Aug 70

Using in situ hybridization, Northern blotting and RT-PCR we studied the post-ischemic expression of bcl-2, bcl-x, bax and ICE. One day following 5 min or 10 min of global ischemia bcl-2 and bcl-x mRNAs were induced in CA1 hippocampal pyramidal neurons while bax was unchanged. By 72 h after ischemia the expression of bcl-2, bcl-x and bax mRNAs decreased in CA1. The large isoform of bcl-x (bcl-xL), detected using RT-PCR, decreased in whole hippocampus by 24-72 h after ischemia relative to the putative short (bcl-xS) and transmembrane deleted (bcl-x delta TM) forms. Oligonucleotides to interleukin-1 beta convertase (ICE), which detected the expected 2-kb transcript and two lesser 1.5- and 3-kb hybridizing species, demonstrated slight mRNA induction in the CA1 region at 72 h following ischemia. DNA nick end-labeling at 3 days following ischemia showed DNA fragmentation in neurons limited to the CA1 region of hippocampus following 5 min ischemia, while DNA fragmentation was detected in CA1, CA3, dentate gyrus and cortical neurons following 10 min ischemia. The data support the view that hippocampal neurons might undergo an apoptosis-like death after global ischemia. Since global ischemia decreases total protein synthesis especially in the CA1 region, the increases in bcl-2 mRNA levels may not necessarily lead to increased Bcl-2 protein levels. This may explain why the CA1 neurons die despite the prominent induction of the protective bcl-2 gene. The observed decrease by 24 h in the bcl-xL/bcl-xS ratio which preceded DNA fragmentation may participate in the cell death produced by ischemia. However, because of the ischemia-induced decrease in total protein synthesis, the decreased bcl-xL/bcl-xS ratio does not necessarily lead to a changed ratio in the amount of the appropriate proteins. Since ICE-like mRNA was induced at 72 h when the CA1 neurons were dead, the significance of this ICE-like mRNA induction remains unclear.
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PMID:Global ischemia induces apoptosis-associated genes in hippocampus. 891 83

Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.
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PMID:Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system. 897 61

To determine the effect of phencyclidine (a noncompetitive NMDA receptor antagonist) on expression of Bax and Bcl-2 (apoptosis-regulating proteins) in gerbil hippocampus after transient forebrain ischemia, brain sections were immunohistochemically evaluated 48, 72, 96 h and 7 days following ischemia. In ischemic control animals, the expression of Bax in CA1 neurons was increased with time and peaked at 72 h, then disappeared at 96 h. In the phencyclidine (5 mg kg-1, intraperitoneally)-treated animals, the intensity of Bax expression at 72 h was weaker than that of ischemic control animals. Furthermore, at 96 h, Bax expression was still observed in CA1 neurons. No expression of Bcl-2 in the CA1 neurons was detected in either control or phencyclidine-treated animals. From these results, it is possible that NMDA receptor antagonists exert their preventive effect against delayed neuronal death through inhibition of Bax protein expression, although the precise relationship between the function of Bax protein and delayed neuronal death is still unclear.
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PMID:Expression of Bax and Bcl-2 protein in the gerbil hippocampus following transient forebrain ischemia and its modification by phencyclidine. 942 65

Recent research indicates that apoptotic mechanisms may be involved in cell death in Alzheimer's disease (AD). We studied the expression of three members of the Bcl-2 protein family, Bcl-2, Bcl-x, and Bax, in a selection of senile and DS-related AD patients as well as in controls. These proteins are all associated with apoptotic mechanisms. In contrast to previous reports, neuronal Bcl-2 labeling was not detected in our cases, although there was some weak and inconsistent glial cell labeling. Neuronal Bcl-x expression was virtually absent in controls and the presence of the protein in AD patients was neither consistent nor specific. Some reactive glial cells were strongly labeled with the Bcl-x antibody. In contrast Bax, a protein that is believed to promote apoptosis, was widely expressed by neurones but was mainly present in areas other than CA1 in the hippocampus. Neuritic elements of some senile plaques were clearly and strongly labeled with this antibody, whereas neurofibrillary tangles and neuropil threads were not. Double labeling studies indicated that AT8-positive cells and neurites were never Bax-positive and vice versa. The possible implications of the different expression patterns are discussed in relation to neurone death in AD.
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PMID:Apoptosis-related protein expression in the hippocampus in Alzheimer's disease. 946 Oct 54

Delayed neuronal death was produced in the CA1 area of the hippocampus following 5 min of forebrain ischemia in adult gerbils. Immunohistochemistry and Western blotting to Bcl-2, Bax, and Bcl-x was examined in control (age-matched, non-operated and sham-operated) and ischemic gerbils. Bcl-2 immunoreactivity was low in CA1 neurons, but Bax was highly expressed in CA1 neurons of control gerbils. Moderate Bcl-x immunoreactivity was observed in control CA1 neurons. Strong Bcl-2 and Bcl-x immunoreactivity was found in CA1 neurons following ischemia. Bcl-2, Bax, and Bcl-x were localized in dying cells, thus suggesting that expression of Bcl-2 was not sufficient to prevent nerve cells from dying. Although the Bcl-x antibody does not discriminate between Bcl-xL and Bcl-xS content in tissue sections, Western blots disclosed a marked increase in the intensity of the band corresponding to Bcl-xS, but not of the band corresponding to Bcl-xL in ischemic hippocampi, thus indicating that the increase in Bcl-xS is associated with delayed cell death following transient forebrain ischemia in the adult gerbil.
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PMID:Bcl-2, Bax, and Bcl-x expression in the CA1 area of the hippocampus following transient forebrain ischemia in the adult gerbil. 969 85

Delayed neuronal death in the gerbil hippocampal CA1 sector occurs 48 to 72 hours after severe forebrain ischemia. DNA fragmentation is observed in the hippocampal CA1 neurons at around that time. We show here that an inhibitor of proteolytic process of apoptosis, N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK), protected hippocampal neuronal damage by inhibition of the DNA fragmentation in a dose-dependent manner and that TPCK induced an apoptosis-regulating molecule, Bcl-2 protein, in the surviving neurons. These results suggest the prevention of apoptosis-related DNA fragmentation by TPCK may be an attractive therapeutic strategy for preserving hippocampal neurons from ischemic insult.
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PMID:Protective effect of apoptosis-inhibitory agent, N-tosyl-L-phenylalanyl chloromethyl ketone against ischemia-induced hippocampal neuronal damage. 970 42


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