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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bcl-2 is the founder member of a growing family of cytoplasmic proteins that modulate the responses of many cell types to the diverse extracellular signals that affect their survival. Although knowledge of the functions of these proteins has come largely from studying cells of the immune system, increasing evidence implicates these proteins in modulating neuronal survival. Several of these proteins are expressed in the nervous system, and experimental overexpression of Bcl-2 prevents the death of neurones deprived of particular neurotrophic factors in vitro, and rescues developing neurones that would otherwise die in vivo.
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PMID:The Bcl-2 family of proteins, and the regulation of neuronal survival. 748 98

We used the intragastric feeding rat model to investigate the relationship between severity of alcoholic liver injury, apoptosis, bcl-2 protein expression, and lipid peroxidation. Rats were fed ethanol with different dietary fats (saturated fat, corn oil, and fish oil) for a 1-month period. Apoptosis was evaluated using an immunohistochemical method, and flow cytometry. Bcl-2 protein concentrations in liver were evaluated by Western blot analysis and lipid peroxidation by measurement of conjugated dienes. Pathological changes (fatty liver, necrosis, and inflammation) were present in corn oil-ethanol and fish oil-ethanol groups only. The highest number of apoptotic cells were seen in the group of rats exhibiting liver injury. The fish oil-ethanol-fed group had the highest concentrations of bcl-2 protein; this protein was localized in the bile duct epithelial and inflammatory cells. A significant correlation was seen between bcl-2 protein assessed densitometrically and the number of inflammatory cells/mm2 (r = 0.78, p < 0.02) and conjugated diene levels (r = 0.82, p < 0.01). Increased numbers of apoptotic cells were seen in rats developing ethanol-induced pathological liver injury. Increased bcl-2 protein concentration are associated with the presence of inflammatory cells and lipid peroxidation.
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PMID:Apoptosis and bcl-2 protein expression in experimental alcoholic liver disease in the rat. 748 30

The immune system provides a useful model system in which to study the signal transduction events involved in the regulation of programmed cell death. Mature lymphocytes have the capacity to survive in the body for prolonged periods of time. During an immune response, cells of the appropriate antigenic specificity must undergo clonal amplification to mount a protective response, and cells participating in inflammatory immune responses need to have the capacity to survive at sites of inflammation. However, upon completion of a successful inflammatory response, the majority of cells produced must die off in order to maintain the homeostasis of the organism. Over the last several years we have learned a great deal about how mature lymphocytes regulated their susceptibility to undergo programmed cell death. Three types of information appear to be used by the lymphocyte to control its susceptibility to undergo programmed cell death. The intrinsic susceptibility of a cell to undergo programmed cell death is determined by members of the Bcl-2 gene family. In addition, extrinsic survival factors, such as IL-2, can initiate signal transduction events that can prevent a cell from initiating apoptosis. Finally, lymphocytes appear to have specific receptors, such as Fas, that can directly induce programmed cell death upon ligand binding. The integration of these three systems is discussed.
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PMID:Receptors that regulate T-cell susceptibility to apoptotic cell death. 748 1

This paper reviews the information concerning immunological memory T and B cells. It shows that the existence of different or a single lineage of memory and naive cells is still a question. The recirculation pattern of memory cells is different from naive cells. A unique recirculation for memory T or B cells is suggested while the bcl2 gene expression possibly plays role in the longevity of memory cells. Various phenotypic markers are demonstrated only on memory or on naive cells; however, a reliable and convenient method for the detection of memory cells still needs to be explored.
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PMID:Characterization of immunological memory cells. A minireview. 748 49

The distribution of Bcl-2 oncoprotein was studied immunohistochemically in formaldehyde-fixed and paraffin-embedded reactive and neoplastic lymphoid tissue. The potential of Bcl-2 for the differential diagnosis of follicular lesions was emphasized, and the results on follicular lesions were correlated with those of polymerase chain reaction (PCR) assay of the immunoglobulin heavy chain gene rearrangement. In hyperplastic lymphoid tissue, Bcl-2 reactivity was widespread, including germinal center surroundings, scattered cells within the germinal centers, and the T-cell areas in general. Distinctively negative lymphoid populations included the majority of germinal center cells, and the negative staining pattern was maintained in cases of florid hyperplasia. In contrast, follicular lymphoma cells were consistently Bcl-2 positive. The immunohistochemical Bcl-2 reactivity of lymphoma follicles correlated with the clonal PCR amplification pattern of the immunoglobulin heavy chain gene; all Bcl-2-negative hyperplasias revealed a non-clonal pattern. Clusters of monocytoid B cells were Bcl-2 negative, whereas monocytoid B-cell lymphomas and closely related MALT lymphomas were positive. All other small cell non-Hodgkin's lymphomas of B-cell types showed nearly uniform Bcl-2 reactivity, whereas large cell B-cell lymphomas were variably positive (74%). In Hodgkin's cells, Bcl-2 reactivity was seen in the neoplastic populations of most cases of nodular sclerosis and mixed cellularity types, whereas the L&H and Reed-Sternberg cells in lymphocyte predominance Hodgkin's disease were negative in most cases. Bcl-2 immunohistochemistry thus appears very valuable in the differential diagnosis of follicular hyperplasia and neoplasia, and it may help to distinguish between reactive and neoplastic monocytoid B cells. However, Bcl-2 immunohistochemistry is not useful in the subtyping of B-cell lymphomas.
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PMID:Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphomas but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferations is of diagnostic value. 748 87

Cell-free systems are valuable tools for the dissection of complex cellular processes. Here we show that cytoplasmic extracts from cells exposed to anti-Fas antibody or UV radiation contain an activity capable of reproducing morphological changes typical of apoptosis in nuclei added to these extracts, as well as internucleosomal cleavage of DNA and proteolysis of a protein known to be cleaved during the apoptosis of intact cells. Extracts from control cell populations were inactive in this respect. These effects were partly blocked by the addition of purified Bcl-2 protein or a competitive inhibitor peptide of interleukin-1 beta-converting enzyme to the extracts. Furthermore, apoptotic activity was induced in cytoplasmic extracts from untreated cells by the addition of ceramide, a lipid second messenger implicated recently in apoptosis signaling. These extracts should prove highly useful in the dissection of molecular events that occur during apoptosis.
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PMID:Cell-free reconstitution of Fas-, UV radiation- and ceramide-induced apoptosis. 748 8

Fas is a type I membrane protein and its activation by binding of the Fas ligand or an agonistic anti-Fas antibody induces apoptosis in Fas-bearing cells. In this report we prepared lysates from cells treated with anti-Fas antibody. The lysates induced apoptotic morphological changes in nuclei from normal mouse liver, accompanied by DNA degradation. The apoptosis-inducing activity was quickly generated in cells by anti-Fas antibody and was found in the soluble cytosolic fraction. Induction of the activity in cells was inhibited by a tetrapeptide, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, a specific inhibitor of interleukin-1 beta converting enzyme. Addition of COS cell lysates containing Bcl-2 to the assay significantly inhibited the apoptotic process, indicating that the in vitro process reflected apoptosis that occurs in intact cells.
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PMID:Apoptosis by a cytosolic extract from Fas-activated cells. 748 9

In a screen of 67 monoclonal antibodies (mAb) included in the Blind Panel of B cell antibodies for the 5th International Workshop on Human Leukocyte Differentiation Antigens, only the CD20 mAb--included as a positive control for immunophenotyping studies--was found to suppress the spontaneous apoptosis which occurs in human germinal center (GC) B cells when placed in tissue culture at 37 degrees C. Further detailed study using the 1F5 mAb confirmed this observation, showing that rescue from apoptosis via CD20, while not as efficient as that obtained on ligating CD40, was of similar magnitude to that achieved on engagement of surface immunoglobulin (sIg) by immobilized antibody. Also similar to anti-Ig, the CD20 mAb rescued from apoptosis without priming for the proliferation of GC B cells: this was quite different to its action on resting, non-GC B cells, where it provides a potent priming signal for cell cycle progression in response to IL-4 or anti-CD40. Unlike the survival signal engendered via sIg, CD20 engagement neither mobilized Ca2+ from intracellular stores or opening of a Ca2+ channel with 1F5, nor did it affect the ability of anti-Ig to open a Ca2+ gate in GC B cells. An unexpected feature of CD20-mediated rescue of GC B cells from apoptosis was a failure to turn on Bcl-2 expression.
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PMID:Engagement of CD20 suppresses apoptosis in germinal center B cells. 748 58

Incubation with the Bcl-2 antibody before fixation of tissues allowed good localization of the antigenic determinant. We showed that the Bcl-2 gene product in centroblastic-centrocytic lymphoma is mainly localized on the outer mitochondrial membrane and, to a lesser degree, on the nuclear envelope. No significant staining was found in other cytoplasmic domains. Careful examination also revealed that gold particles did not recognize an integral membrane epitope, but an antigenic determinant localized at a short distance from the cytoplasmic side of the membrane itself. This observation suggests that, by interacting with other cytoplasmic proteins, Bcl-2 plays some role in the cytoplasmic machinery involved in the regulation of programmed cell death.
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PMID:Localization of the Bcl-2 protein to the outer mitochondrial membrane by electron microscopy. 749 35

It appears that the switch recombination machinery of a B lymphocyte targets preferentially unrearranged heavy chain genes that have been rendered transcriptionally active. Transcriptional activation of the 'germline' human C alpha 1 and C alpha 2 genes is triggered by TGF-beta 1 and is controlled by proximal positive and distal negative regulatory elements residing upstream of the alpha 1 and alpha 2 switch regions respectively. In this report we characterize the positive proximal regulatory elements and analyse their interaction with DNA binding proteins. Our data demonstrate that a 100 bp fragment that contains a cAMP responsive element (CRE)/activating transcription factor (ATF) motif, a putative Ets binding site and an element that is created by two previously described neighbouring direct repeats (DRE), can increase the basal level of transcription and confer TGF-beta 1 inducibility to a heterologous promoter in an orientation- and position-independent manner. Ubiquitously expressed DNA binding proteins interact specifically with the CRE/ATF, the Ets site and the DRE element. Additionally, nuclear proteins interact with sequences which are located downstream of this enhancer are not essential for transcription in the transient expression assays utilized; however, they contain motifs that have been previously implicated in regulating DNA recombination events. These motifs include a Chi motif and a Chi-like element previously found in the recombination hotspot region of the Bcl-2 proto-oncogene and close to chromosomal breakpoints in T-ALL lines. Our findings raise the possibility that the intervening region associated regulatory elements in addition to regulating the transcriptional activation of the Ig heavy chain genes could also facilitate the physical interaction of transcription and recombination controlling molecular mechanisms.
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PMID:The human I alpha 1 region contains a TGF-beta 1 responsive enhancer and a putative recombination hotspot. 749 26


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