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 gene product of open reading frame 5 (p25) of porcine reproductive and respiratory syndrome (PRRS) virus has been expressed by coinfection of culture cells with vaccinia virus expressing the T7 RNA polymerase and a recombinant vaccinia virus encoding the open reading frame 5 gene under the T7 promoter and the encephalomyocarditis virus internal ribosome entry site. In spite of the reported efficiency of the expression system, very poor accumulation of p25 protein was observed and a strong cytotoxicity was produced in the doubly infected cells. This cell toxicity was shown to occur by induction of apoptosis, as indicated by nucleosome ladder formation, chromatin condensation, and rRNA degradation. Apoptosis induction was also observed after infection of cultured cells with an adapted PRRS virus strain and after infection of swine macrophage cells with a PRRS virus field strain. Contrary to the observations made for other cases of virus-induced apoptosis, we could not prevent p25 protein-induced apoptosis by using a cell line permanently expressing Bcl-2 protein.
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PMID:Open reading frame 5 of porcine reproductive and respiratory syndrome virus as a cause of virus-induced apoptosis. 862 62

The generation of ceramides by the action of acidic and/or neutral sphingomyelinases has been implicated in many forms of apoptosis. We investigated whether exposure to ceramides is sufficient to induce apoptosis in human leukemia cells and, if so, what the characteristics of this form of apoptosis might be. Treatment of the acute lymphoblastic T-cell line CEM-C7H2 with short- and medium-chain ceramide analogs (C2-, C6-, and C8-ceramide) resulted in apoptosis, whereas the inactive C2-dihydroceramide had no effect on cell survival. Induction of apoptosis was relatively slow (approximately 40% after 24 h) and required high concentrations of ceramide analogs (40-100 microM). To investigate a possible involvement of interleukin 1-beta-converting enzyme (ICE) or ICE-related proteases, we treated CEM-C7H2 sublines constitutively expressing the vaccinia virus protease inhibitor crmA with ceramide analogs. Although such cells were completely resistant to apoptosis induced by antibodies to the Apo-1/Fas surface receptor (a form of apoptosis known to be inhibitable by CrmA), they were not protected from ceramide-induced cell death. In contrast, tetracycline-regulated overexpression of Bcl-2 protected CEM-C7H2 sublines stably transfected with corresponding constructs from ceramide-induced apoptosis. Thus, in these human leukemia cells, ceramides induce a relatively slow death response that can be prevented by Bcl-2, but is independent of CrmA-inhibitable proteases. These characteristics distinguish ceramide-induced from other forms of apoptosis, such as Apo-1/Fas-induced cell death where ceramide production has been causally implicated.
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PMID:Ceramides induce a form of apoptosis in human acute lymphoblastic leukemia cells that is inhibited by Bcl-2, but not by CrmA. 900 May 5

Toxic effects of nitric oxide (NO) were suggested to be mediated by its metabolite peroxynitrite, a strong oxidizing agent. To determine if antioxidative effects of Bcl-2 protooncogene can prevent NO-mediated apoptosis, we used vaccinia virus recombinants expressing mouse inducible NO-synthase, iNOS, or human bcl-2 genes. Expression of iNOS in HeLa G cells induces apoptosis which can be prevented by co-expression of bcl-2 or by addition of reduced glutathione or N-acetylcysteine. We demonstrate that this NO-induced apoptosis proceeds through the activation of interleukin-1 beta-converting enzyme-like proteases and cleavage of the poly(ADP-ribose) polymerase, an effect which is also prevented by Bcl-2.
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PMID:Bcl-2 prevents nitric oxide-mediated apoptosis and poly(ADP-ribose) polymerase cleavage. 909 16

The interferon (IFN)-induced enzyme RNase L produced by a recombinant vaccinia virus (VV) causes death of mammalian cells with morphological and biochemical characteristics of apoptosis. Coexpression of 2-5A-synthetase enhances apoptosis induced by RNase L Activation of endogenous RNase L by infection with a VV ts mutant (ts22) or with wild-type virus in the presence of the antipoxvirus drug isatin-beta-thiosemicarbazone, a treatment known to significantly increase the amount of double-stranded RNA late during infection, also causes pronounced apoptosis of infected cells. The effects observed with recombinant virus-derived RNase L or with the endogenous enzyme are specific, since apoptosis also occurs in cells derived from mice lacking the IFN-induced protein kinase (PKR). The apoptosis antagonist Bcl-2 prevents induction of cell death by RNase L activation. Apoptosis of mammalian cells by RNase L activation could be a mechanism mediating anticellular actions of IFN.
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PMID:Activation of the IFN-inducible enzyme RNase L causes apoptosis of animal cells. 932 43

Poxviruses express a number of host range (hr) genes that control virus growth in distinctive cell types. Inactivation of hr gene expression in several reported cases has led to apoptosis of virus-infected cells. In RK13 cells, the K1L gene serves as a hr gene for vaccinia virus. We therefore investigated the effect of K1L expression in apoptosis of RK13 cells. In contrast to other hr genes, no significant increase of apoptosis was detected in RK13 cells infected with a K1L- mutant virus. Also, expression of a CHO hr gene CP77 rescues K1L- mutant virus in RK13 cells with little effect on apoptosis. We then set out an experimental approach to investigate the relationship between apoptosis and host restriction in CHO and RK13 cells. A recombinant vaccinia virus expressing a human bcl-2 gene, bcl2-VV, was constructed. Expression of bcl-2 suppressed apoptosis of virus-infected CHO cells as expected. However, bcl-2 expression did not allow virus growth in CHO cells, suggesting apoptosis suppression is not sufficient to rescue host restriction. Moreover, infection of bcl-2VV in RK13 cells induced significant apoptosis with no reduction on virus production, indicating that apoptosis does not contribute to host restriction. In consideration of this data, we conclude that host restriction of vaccinia virus in CHO and RK13 cells is mediated by a pathway distinct from apoptosis.
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PMID:Apoptosis and host restriction of vaccinia virus in RK13 cells. 949 28

Apoptosis is a form of physiological cell death which can be initiated in response to various stimuli including virus infections. We show that vaccinia virus (VV) infection induces apoptosis in an immature B lymphocyte line, WEHI-231. In these cells, several VV-specific proteins were synthesized during the infection, but neither virus production nor viral DNA synthesis were detected. The intracellular levels of the proto-oncogene Bcl-2, which effectively protects cells from programmed cell death, were found to be down-regulated by the VV infection, suggesting that this down-regulation might be involved in the viral induction of apoptosis in WEHI-231 cells. Stable transfectants overexpressing human Bcl-2 were shown to be resistant to the apoptosis produced by the infection, a finding consistent with the proposed role for the down-regulation of endogenous Bcl-2 in VV-induced apoptotic death.
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PMID:Vaccinia virus-induced apoptosis in immature B lymphocytes: role of cellular Bcl-2. 987 67

In animals, T cells often die rapidly after activation, unless activation occurs in the presence of inflammatory factors. To understand how such activated cells survive to participate in immune responses, we studied the effects of viral infection on T cells responding to an unrelated superantigen. Normal T cells activated by superantigen in uninfected mice died as a result of their activation, whereas T cells that were activated during vaccinia infection survived longer in vivo and in culture. This bystander effect of viral infection on activated T cells was independent of effects on the magnitude of the initial T cell response, on induction of Bcl-2 and Bcl-x, on T cell proliferation, and on Fas killing. The failure of such effects to predict the fate of activated T cells in vivo indicates that virus infections shape T cell responses via mechanisms that differ from those described previously. These mechanisms may contribute to the ability of viral infections to induce autoimmunity.
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PMID:Bystander virus infection prolongs activated T cell survival. 1020 91

We demonstrated that infection of 17Cl-1 cells with the murine coronavirus mouse hepatitis virus (MHV) induced caspase-dependent apoptosis. MHV-infected DBT cells did not show apoptotic changes, indicating that apoptosis was not a universal mechanism of cell death in MHV-infected cells. Expression of MHV structural proteins by recombinant vaccinia viruses showed that expression of MHV E protein induced apoptosis in DBT cells, whereas expression of other MHV structural proteins, including S protein, M protein, N protein, and hemagglutinin-esterase protein, failed to induce apoptosis. MHV E protein-mediated apoptosis was suppressed by a high level of Bcl-2 oncogene expression. Our data showed that MHV E protein is a multifunctional protein; in addition to its known function in coronavirus envelope formation, it also induces apoptosis.
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PMID:Induction of apoptosis in murine coronavirus-infected cultured cells and demonstration of E protein as an apoptosis inducer. 1043 79

Using a recombinant vaccinia virus expressing protooncogene Bcl-2, we demonstrate opposite effects of the expressed Bcl-2 in two cell lines: apoptosis induction in BSC-40 cells and apoptosis prevention in HeLa G cells. The apparent molecular weight of the expressed Bcl-2, its amounts and its effects on the mitochondrial membrane potential are comparable in both cell lines, suggesting that the consequences of Bcl-2 expression depend on the cellular environment. To further support these findings we demonstrate the pro-apoptotic effect of the expressed Bcl-2 in several other cell lines.
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PMID:Protooncogene Bcl-2 induces apoptosis in several cell lines. 1187 56

Vaccinia virus (VV) infects a broad range of host cells, and while it usually causes their lysis (i.e. necrosis), the nature of the cell-death phenomenon is not well understood. In this study, we show that VV induces apoptosis of cells of the murine macrophage line J774.G8, as revealed by morphological signs, DNA ladder formation, changes of mitochondrial membrane potential and annexin-V positivity. Apoptosis occurred in both untreated and IFN-gamma-pretreated macrophages, and could not be inhibited by aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase. Inhibition of VV DNA synthesis and late gene expression by cytosine arabinoside also did not prevent apoptosis, while heat- or psoralen/UV-inactivated VV did not cause any apoptosis. Thus, VV early gene expression seems to be required for induction of apoptosis. At the cellular level, infection with VV induced a decrease in the levels of Bcl-x(L), an anti-apoptotic member of the Bcl-2 family. The importance of loss of Bcl-x(L) was demonstrated by prevention of VV-mediated apoptosis on expression of Bcl-2, a functional homologue of Bcl-x(L). Our findings provide evidence that induction of apoptosis by VV in macrophages requires virus early gene expression, does not involve nitric oxide, induces a decrease in mitochondrial membrane potential and is associated with altered levels of Bcl-x(L).
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PMID:Vaccinia virus induces apoptosis of infected macrophages. 1238 19


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