Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial lymphoma is uncommon and is usually associated with various forms of hereditary immunodeficiencies. Primary gastric lymphomas that occurred in three adults from the same family, who had no overt immunodeficiency or cancer of non-lymphomatous origin, are reported. Two sisters presented with a low grade lymphoma of the mucosa associated lymphoid tissue type. Their father presented with a high grade form of later onset. All lymphomas have been phenotypically characterised as being of B cell origin. Epstein-Bar virus DNA was detected by polymerase chain reaction in the biopsy specimen of the high grade lymphoma but bcl-2/JH protooncogene rearrangement, t (14:18), was not identified in either the low or high grade lymphoma specimens tested.
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PMID:Familial primary gastric lymphoma. 843 45

Most studies of apoptosis on T lymphocytes have examined the effects of various stimuli on immature T cells from the thymus. Previous work has indicated that apoptosis of mature memory T cells may be an important pathophysiologic mechanism in diseases such as AIDS, cancer, and autoimmunity. The effect of IL-2 on apoptosis of T cells is not clear. Therefore, we studied the ability of IL-2 to rescue Ag-specific T cells from apoptosis. We found that IL-2, in a dose-dependent manner, prevented T cells from entering apoptosis induced by gamma-irradiation, mitomycin C, or dexamethasone. This effect was specific for IL-2; IL-1 beta, IL-6, or IFN-gamma could not reproduce it. In contrast to Ag-specific T cells, immature T cells and naive mature peripheral T cells could not be rescued by IL-2 from radiation-induced apoptosis. Apoptosis rescue by IL-2 was associated with the induction of bcl-2 mRNA and protein. This induction could not be attributed to the effects of IL-2 on the cell cycle, as T cells that were prevented from cell cycle progression by irradiation showed a similar induction of bcl-2. Rescued cells retained their Ag-specific proliferative capacity and in vivo functions. These findings demonstrate that the apoptotic death of Ag-specific T cell lines, cells which can be regarded as a model for memory T cells, can be prevented with IL-2. This effect may have important therapeutic implications for patients receiving chemotherapy or radiotherapy, and for patients with AIDS who develop immunodeficiency primarily as a result of loss of Ag-specific memory T cells.
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PMID:IL-2 rescues antigen-specific T cells from radiation or dexamethasone-induced apoptosis. Correlation with induction of Bcl-2. 854 1

Cytokine deprivation from activated T cells leads to apoptosis associated with down-regulation of the bcl-2 gene product. It is not clear, however, how cytokines other than interleukin-2 (IL-2) may affect this process and regulate the involvement of other apoptosis-modulating genes. We show that a group of cytokines including IL-2 (IL-2R gamma), prevent the apoptosis of IL-2-deprived activated T cells. This rescue involves the induction of the anti-apoptosis genes bcl-2 and bcl-xL), but causes little change in expression of bax and bcl-xS, which promote apoptosis. Furthermore, the prevention of apoptosis and induction of proliferation by the common gamma chain cytokines can be dissociated. Thus, when proliferation is blocked, the common gamma chain cytokines still induce up-regulation of bcl-2 relative to bax and retard apoptosis. These cytokines can thus regulate the persistence or removal of effector T cells by coordinating the balance between genes which promote and those which inhibit apoptosis, events which are probably mediated at least in part by signals through the common gamma chain. These data also implicate inappropriate T cell apoptosis resulting from a dysfunctional common gamma-chain as part of the pathophysiological defect in patients with X-linked severe-combined immunodeficiency (SCID).
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PMID:Interleukin-2 receptor common gamma-chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: selective induction of anti-apoptotic (bcl-2, bcl-xL) but not pro-apoptotic (bax, bcl-xS) gene expression. 861 94

The cytopathic effects (CPE) resulting from the infection of CD4+ T cells by human immunodeficiency virus (HIV) have generally been characterized as single-cell killing associated with apoptosis and/or the generation of syncytia resulting from the direct cell-to-cell transmission of the virus. Little is known, however, about the cellular factors influencing host cell susceptibility to HIV-mediated CPE. Because expression of the antiapoptosis gene, bcl-2, enhances cell viability after exposure to cytotoxic agents or stimuli, the effect of bcl-2 expression on HIV infection of stably transfected T-cell clones was investigated. Unexpectedly, bcl-2 expression by these cells accelerated the kinetics of an acute spreading HIV infection, as evidenced by a rapid loss of culture viability associated with the appearance of CPE and reverse transcriptase activity in the culture supernatant. This unexpected effect of bcl-2 expression results from the arrest of syncytial apoptosis, directly facilitating the cell-to-cell transmission of HIV. In addition, bcl-2 expression is associated with enhanced HIV replication as determined by HIV type 1-specific Western blot (immunoblot) analysis. These results suggest that the inhibition of apoptosis is essential for this mode of viral transmission.
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PMID:bc1-2 expression facilitates human immunodeficiency virus type-1 mediated cytopathic effects during acute spreading infections. 867 88

CBA/N mice carry an X-linked immunodeficiency (xid) due to a point mutation in the Bruton's tyrosine kinase (btk) gene. xid mice have a smaller peripheral B cell pool than normal animals, lack CD5+ B cells (B1), and are hyporesponsive to mitogenic anti-Igs and thymus-independent type 2 Ags. The proto-oncogene bcl-2 affects B cell homeostasis by suppressing programmed cell death. We hypothesized that reduced bcl-2 expression could enhance programmed cell death in xid B cells, directly causing poor peripheral B cell survival and indirectly affecting Ag responsiveness. We measured and compared levels of endogenous Bcl-2 protein and spontaneous apoptosis in xid and normal B cells, and determined the effect of a human bcl-2/Ig minigene on B cell survival and Ag responsiveness in bcl-2 transgenics. The amount of endogenous Bcl-2 was reduced fivefold in freshly isolated xid B cells compared with that in normal cells, but was equal in xid and normal T cells. Attrition by spontaneous apoptosis was significantly higher in cultured xid B cells. Expression of the bcl-2 transgene suppressed apoptosis equally in normal and xid B cells, prolonged in vitro survival, and markedly expanded in vivo the follicular B cell population normally reduced in xid mice. However, most xid defects persisted; xid/bcl-2 mice remained deficient in B1 cells and hyporesponsive to anti-Igs, thymus-independent type 1 Ags, and thymus-independent type 2 Ags. The data suggest that signal transduction pathways using Btk independently regulate B cell survival and Ag responsiveness.
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PMID:Regulation of B cell survival in xid mice by the proto-oncogene bcl-2. 869 Sep 3

Infection by human immunodeficiency virus type 1 (HIV-1) is characterized by progressive loss of various cell types, mainly CD4+ T lymphocytes. While a passive role for the virus in cell destruction is recognized, it does not account for the vast amount of cell death including those of uninfected "bystander' cells. Since in the past we and others have demonstrated the capacity of the Tat protein of HIV-1 to modulate the expression of various cellular genes and that Tat secreted by HIV-infected cells can be readily taken up by various cell types, we have investigated the role of Tat on inducing apoptosis. Our results indicate that T lymphocytes transfected to constitutively express HIV-1 tat, when grown under serum-free conditions results in rapid apoptosis characterized by typical ultrastructural features and DNA fragmentation. Additionally, we observed that in several hematopoietic cell types, including T and B lymphoid cells and monocytoid cells, the expression of HIV-1 tat results in down-regulation of bcl-2, an oncogene with known potential for inhibition of apoptosis. The tat-mediated down-regulation of bcl-2 was observed at both the transcriptional and translational levels. Also, tat-transfected cells expressed increased amounts of bax, a bcl-2 family protein known to induce apoptosis. While these results support reports in the literature of an active role for tat in inducing cell death in HIV-infected individuals, they point to a new mechanism involving Tat-mediated modulation of bcl-2 and bax.
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PMID:Expression of human immunodeficiency virus type I tat results in down-regulation of bcl-2 and induction of apoptosis in hematopoietic cells. 876 Feb 90

Expression of the human immunodeficiency virus type 1 (HIV) protease in cultured cells leads to apoptosis, preceded by cleavage of bcl-2, a key negative regulator of cell death. In contrast, a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes, while reducing the yields of viral structural proteins, infectivity, and tumor necrosis factor alpha. We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2, leading to oxidative stress-dependent activation of NF kappa B, a cellular factor required for HIV transcription, and ultimately to cell death. Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113. The results suggest a new option for HIV gene therapy; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site.
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PMID:Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. 879 Mar 71

Homeostasis of cell numbers in tissues is maintained by a critical balance between cell proliferation and programmed cell death or apoptosis. Many human viruses are able to develop suitable strategies for modifying apoptosis in virus-infected cells and in virus-primed T cells. Apoptosis is characterized by the fragmentation of nuclear DNA into 180-200 bp apoptotic bodies and can be analysed microscopically or by flow cytometry using staining with various dyes. Moreover DNA cleavage can be identified by electrophoresis and by specific labeling using in situ nucleotidyltransferase assay (ISNT), terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling technique (Tunel), or by Elisa. Adenovirus E1A induces expression of protooncogenes c-myc and c-fos which sensitize cells to apoptosis; EBV EBNA-5, and adenovirus E1A, HPV E7, and polyomavirus large T act in the same way by displacing pRB-bound E2F. EBV EBNA-5, HPV E6, Adenovirus E1B 55 kDa inactivate the tumor suppressor protein p53 and engage the cells in the transformation process. EBV LMP-1, HHV6, and HTLV1 tax induce the antiapoptotic bcl-2 protein. EBV BHRF1 encodes proteins with homology to bcl-2 and Adenovirus E1B 19 kDa encodes proteins that have protective functions similar to bcl-2. Activated lymphocytes responding to viral infections express high levels of fas and are susceptible to apoptosis. TNF alpha can down- or up-regulate fas and down-regulates TNF-R. Adenovirus E1B 19 kDa blocks the proapoptotic activity of TNF alpha. Inversly, Cytomegalovirus, hepatitis C virus and Myxoviruses up-regulate fas antigen prior to undergoing apoptosis. In HIV-infected patients, CD4+ T-cell apoptosis is mediated by the cytopathic effect of the virus and the cell surface expression of gp 120-env protein. Moreover, an accelerated T-cell apoptosis in HIV-infected individuals is characterized by (i) HIV gp120-CD4+ cross-linking and subsequent aberrant signaling of T-cells, (ii) involvement of TNF alpha-fas/Apo-1 (TNF-R) binding, (iii) involvement of accessory cells as an apoptosis inducer and as a result of defective antigen presentation, (iv) possible superantigen activity induced by HIV products and cofactors. Many viruses also encode proteins with protease activity which could induce apoptosis. The induction of apoptosis may result in virus clearance, in contrast the inhibition of apoptosis may result in virus cell transformation and viral persistence. Indirectly, the apoptosis of infected cells may be induced by CTLs, NK cells and cytokines. In addition, apoptosis-mediated physiological depletion of T lymphocytes in the course of viral infection can silence the immune response and can induce immunodeficiency.
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PMID:[Apoptosis and human viral infections]. 886 58

Tat protein of human immunodeficiency virus type-1 (HIV-1) plays a central role in viral replication and shows pleiotropic effects on the survival and growth of different cell types. Remarkably, Tat represents the first example of a viral protein, that can also be actively secreted by infected cells and shows a cytokine-like activity on both HIV-1 infected and uninfected cells. We previously reported that the stable expression of tat cDNA rescues Jurkat cell lines from apoptosis induced by a variety of stimuli, such as serum withdrawal, engagement of fas antigen or even a productive infection with HIV-1. These findings suggested that Tat was able to modulate the expression of one or more gene(s) relevant for the control of cell survival/death. Consistently, Jurkat cells stably transfected with tat show an upregulated expression of bcl-2. It is still unsettled whether Tat affects cell survival and bcl-2 expression directly or indirectly, modulating the expression of other cellular genes involved in the control of cell survival or encoding for cytokines. Blocking experiments performed with anti-Tat neutralizing antibodies revealed that TAt increases bcl-2 expression and prevent lymphoid T cells from apoptosis by acting, at least in part, through an autocrine/paracrine loop. While high (nM-microM) concentrations of extracellular Tat display a cytotoxic activity on the antigen-mediated induction of T cell proliferation, low (pM) concentrations of Tat were able to protect both Jurkat cells and primary peripheral blood mononuclear cells from apoptosis. Significantly, pM concentrations of Tat were detected in the sera of some HIV-1 infected individuals as well as in the culture supernatant of HIV-1 infected cells, raising the possibility that these levels of Tat protein may be present physiologically in vivo. The potential relevance of Tat-mediated upregulation of bcl-2 for the pathogenesis of HIV-1 disease is discussed.
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PMID:The human immunodeficiency virus type-1 (HIV-1) Tat protein and Bcl-2 gene expression. 903 Oct 86

Fifty-one cases of acquired immunodeficiency syndrome (AIDS)-related primary brain lymphomas (AR-PBL) were investigated for clinical characteristics; human immunodeficiency virus (HIV)-associated disorders; histopathologic features; immunophenotype; Epstein-Barr virus (EBV) infection; and, when frozen tissue was available, oncogene rearrangements. AR-PBL occurred late in the course of AIDS and were usually associated with other systemic or cerebral disorders and with a low level of CD4 lymphocytes. All cases were high grade lymphomas according to the Working Formulation or updated Kiel classification, and often displayed a multifocal pattern. Thirty cases were classified as immunoblastic with plasmacytic differentiation, 18 cases were large cell lymphomas with an immunoblastic component or centroblastic polymorphic lymphomas, and 2 were small noncleaved non-Burkitt lymphomas (Working Formulation). This latter category is classified as Burkitt's-like lymphoma in the REAL nomenclature. One case could not be classified because of necrosis. AR-PBL showed a high level expression of activation and adhesion molecules. The presence of EBV was detected in most cases, and, when PCR was used, this was a constant finding. bcl-2 oncoprotein and latent membrane protein-1 (LMP-1) were strongly expressed. None of the tested cases expressed p53, or were rearranged for bcl-2 or c-myc oncogenes. This study confirms the immunophenotypic specificity of AR-PBL, which may reflect the special immune status of the brain.
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PMID:AIDS-related primary brain lymphomas: histopathologic and immunohistochemical study of 51 cases. The French Study Group for HIV-Associated Tumors. 904 3


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