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 development of a cell culture system efficient in the establishment of lymphoma cell lines has made it possible to dissect basic biological and molecular aspects of lymphoma cells. We have established a lymphoma cell line from a patient with B cell lymphoma. The cell line has a complex karyotype with translocations involving bands 8q24, 14q32, and 18q21. Molecular analysis revealed that the Myc gene was rearranged; we were unable to demonstrate rearrangement of the Bcl-2 gene. Evaluation of the structure of the heavy chain Ig genes revealed that the cell line carried the same rearrangements as the cells from which the cell line was derived. The pattern of rearrangement, however, was unusual in that there were at least four rearranged bands when DNA cut with HindIII was probed with a fragment of the heavy chain joining region. To further characterize the cell line, subclones were derived. Individual subclones had the same pattern of rearrangement as the parent cell line. The results of these studies provide evidence that multiple rearranged Ig genes may be present in a single clone of cells.
J Clin Invest 1992 Mar
PMID:A human lymphoma cell line with multiple immunoglobulin rearrangements. 131 15

The last decade has seen major advances in the acquisition of knowledge concerning both the cellular and molecular genetics of multiple myeloma. Although discrete and specific changes associated with the plasma cell disorders have yet to be identified, a pattern is emerging that one can associate with the plasma cell disorders. This pattern includes the frequent involvement of chromosomes 1 and 14, and in particular presence of the 14q+ abnormality. But in addition there are typically many other numeric and/or structural changes that can, in fact, involve almost any chromosome, but particularly chromosomes 3, 5, 6, and 7, as well as 11, 14, 17, and 18. The presence of one or more unidentified marker chromosomes is also a typical feature. The ongoing challenges include identification of a crucial initial genetic change (if such exists) as well as the factors contributing to the ongoing karyotypic evaluation that results in complex karyotypes in patients with advanced disease. There is no doubt that the complex karyotypic picture contributes to the major heterogeneity of plasma cells that occurs in malignant plasma cell disorders. Karyotypic complexity underlies heterogeneity in cell morphology, surface antigen expression, response to cytokines, and a variety of other functional characteristics. The aberrant expression of antigens normally found on other hematopoietic progenitors has led to speculation about the true nature of the stem cell in myeloma. The overriding challenge, however, is to fully understand the plasma cell disorders at the molecular level. Although changes have already been noted in the functions of C-myc, the ras family of oncogenes, Bcl-2 expression, and several so called anti-oncogenes such as p53, it is likely that we have only begun to scratch the surface in the area of molecular changes. The potential for involvement at multiple molecular sites and the possibility of complex interactions between gene segments is truly overwhelming. However, it is hoped that at the molecular level a pattern will ultimately emerge. It is most interesting, as previously discussed, that there is an interplay among C-myc, N-ras, Bcl-2, and the Epstein-Barr virus in the predilection for a plasma cell phenotype. Undoubtedly there is much more to learn, and it is truly exciting to finally have some tools and probes at hand to more effectively study the genome in multiple myeloma and related disorders.
Hematol Oncol Clin North Am 1992 Apr
PMID:Cellular and molecular genetic features of myeloma and related disorders. 158 85

We examined the expression of the Bcl-2 gene at chromosome segment 18q21, that is translocated into the Ig heavy chain gene locus in t(14;18) bearing lymphomas. Bcl-2, while B cell associated, is expressed in a variety of hematopoietic lineages including T cells. Bcl-2 mRNA levels are high during pre-B cell development, the time at which the t(14;18) translocation occurs, but are down regulated with maturation. Like certain other oncogenes, Bcl-2 is quiescent in resting B cells but up-regulated with B cell activation. Mature B cell lymphomas with a t(14;18) have log-folds more mRNA than matched counterparts without the translocation. A sensitive S1 protection assay revealed that all transcripts in t(14;18) B cells were Bcl-2-Ig fusion mRNAs and originated from the translocated allele. Thus, there is a marked deregulation of Bcl-2 when it is introduced into the Ig locus in t(14;18) lymphomas.
J Clin Invest 1987 Nov
PMID:Expression of Bcl-2 and Bcl-2-Ig fusion transcripts in normal and neoplastic cells. 350 Jan 84

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.
Alcohol Clin Exp Res 1995 Aug
PMID:Apoptosis and bcl-2 protein expression in experimental alcoholic liver disease in the rat. 748 30

We investigated the modulation of radio- and chemoresistance by caffeine and mechanisms of resistance in human leukemic cell lines and mononuclear cells from 18 leukemic patients. Caffeine synergistically potentiated cytotoxicity and apoptosis induced by ionizing radiation or carboplatin (CPt), but attenuated induction of apoptosis by daunorubicin (DNR) in KG-1a cells. Since caffeine released irradiated as well as DNR-treated KG-1a cells from G2M cell cycle arrest and CPt-treated cells from S-phase arrest, this release does not fully explain the different effects of caffeine. Caffeine synergistically reduced the level of the apoptosis inhibitor glutathione after irradiation or CPt treatment. In contrast, treatment with DNR plus caffeine diminished glutathione levels to a lesser extent than DNR alone. We conclude that the effect of caffeine on glutathione depletion represents a mechanism of action by which caffeine can modulate apoptosis. Caffeine increased CPt cytotoxicity in K562 cells and its doxorubicin-resistant subline (K562/ADM), but little effect was seen in HL-60 cells or mononuclear cells from leukemic patients. Multivariate cluster analysis revealed an association of CPt resistance with the expression of c-Fos, c-N-Ras, and p53 oncoproteins and with proliferative activity (S-phase of cell cycle), but not with Bcl-2 expression.
J Cancer Res Clin Oncol 1995
PMID:Expression of apoptosis-related oncoproteins and modulation of apoptosis by caffeine in human leukemic cells. 759 28

Incubation of ex vivo cultured mature B cells in the presence of nitric oxide or nitric oxide-donor substances delays programmed cell death as determined by the appearance of DNA laddering in agarose gel electrophoresis or by flow-cytometry analysis of DNA. Nitric oxide also rescues B cells from antigen-induced apoptosis but fails to provide a co-stimulatory signal that converts the signal elicited by the antigen into a proliferative response. The protective effects of nitric oxide against programmed cell death can be reproduced by treatment of the cells with permeant analogues of cyclic GMP. Regarding the mechanisms by which nitric oxide prevents apoptosis in B cells, we have observed that nitric oxide release prevents the drop in the expression of the protooncogene bcl-2, both at the mRNA and protein levels, suggesting the existence of an unknown pathway that links nitric oxide signaling with Bcl-2 expression.
J Clin Invest 1995 Apr
PMID:Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels. 770 95

Chronic B lymphocytic leukemia cells (B-CLL), characterized by the accumulation in vivo of long-life span B cells, exhibit spontaneous programmed cell death or apoptosis when cultured in vitro. We show that interferon-alpha (IFN-alpha), although able to decrease in vivo the number of leukemic cells, protects chronic B lymphocytic leukemia cells from in vitro programmed cell death or apoptosis. This inhibition of spontaneous in vitro apoptosis of leukemic B cells was observed after 24-48 hr of culture with 100-1000 U of either Interferon-alpha 2a or 2b. The protective activity was observed in the majority of the patients tested (6 out of 8) independent of the amount of apoptosis observed. Furthermore, in contrast to IL-4, IFN-alpha did not up-regulate the expression of Bcl-2. This suggests that B-CLL cells can be prevented from undergoing apoptosis in vitro by at least two different mechanisms: one, triggered for instance by IL-4, is associated with Bcl-2 production and the second triggered by Interferon-alpha is Bcl-2 independent. To elucidate the pathways mobilized by Interferon-alpha we also studied the regulation of c-myc expression in our experimental system. We found that (i) induction of in vitro B-CLL apoptosis was not associated with up-regulation of c-myc, (ii) c-myc expression as assessed by mRNA and protein determinations was increased after in vitro or in vivo Interferon-alpha stimulation. Additional experiments using c-myc specific oligonucleotides demonstrated that when Interferon-alpha-mediated c-myc expression was decreased by 60%, the in vitro protective effect of Interferon-alpha was not modified. Thus our data show that in contrast to the situation in vivo, Interferon-alpha prevents spontaneous in vitro B-CLL cells apoptosis through a Bcl-2-independent pathway which is probably not related to c-myc up-regulation.
Clin Immunol Immunopathol 1994 Nov
PMID:Interferon-alpha-mediated prevention of in vitro apoptosis of chronic lymphocytic leukemia B cells: role of bcl-2 and c-myc. 792 26

1. Over 100 different agents have been shown, under certain circumstances, to cause apoptosis, a form of cell death with characteristic morphology. In most cases, the mechanism of cell death is likely to be the same, as expression of the cell death inhibitory gene bcl-2 can frequently prevent apoptotic changes and/or delay cell death. 2. These observations raise the question of how and why cells detect these agents and why they respond by implementing the suicide mechanism that bcl-2 can control. Our hypothesis is that apoptosis is used as an anti-viral strategy, and that cells interpret any metabolic disturbance as evidence of infection by a virus and thereby kill themselves in response to these toxins before they are killed by the action of the toxin itself. 3. Experiments on the effect of sodium azide upon growth factor-dependent cells support this idea. Bcl-2 can delay cell death caused by azide, and inhibit apoptotic changes seen by electron microscopy, but cannot prevent the eventual death of the cells. 4. These ideas suggest that drugs designed to regulate cell death may be useful for the treatment of ischaemic or neoplastic diseases. For example, human cells may activate a suicide pathway in response to sub-lethal amounts of anoxia following a stroke or heart attack and so blocking apoptosis may be a useful therapy to limit tissue damage. On the other hand, increasing the propensity of cells to activate their physiological cell death mechanisms may enhance the effectiveness of toxins designed to kill tumour cells.
Clin Exp Pharmacol Physiol 1995 Nov
PMID:Hypothesis: apoptosis caused by cytotoxins represents a defensive response that evolved to combat intracellular pathogens. 859 45

The expression of apoptosis-regulating proteins, Bcl-2, Bax, Mcl-1, and Bcl-X, was evaluated by immunohistochemical methods in 39 cases of thyroid carcinomas. Normal thyroid tissues showed a consistent expression of Bcl-2 and Mcl-1 whereas Bax and Bcl-X proteins were essentially absent from most follicular thyroid cells. Bax expression was observed in all papillary carcinomas (n = 23) and in 8 of 10 follicular carcinomas. The intensity of Bcl-2 immunostaining was generally higher in follicular tumors (n = 10) than in papillary carcinomas (n = 21 of 23). However, in undifferentiated tumors, both Bax and Bcl-2 were weakly expressed. Mcl-1 protein expression was similar to that of Bax in papillary and follicular tumors, but was also frequently detectable in undifferentiated tumors. Bcl-X immunostaining was seen in all undifferentiated tumors (n = 6), in 22 of 23 papillary tumors, and in 5 of 10 follicular tumors. Our findings show that the regulation of bcl-2 family gene expression is different in normal thyroid tissue compared to that of its neoplastic counterpart and varies with the tumor subtype. In particular, unlike normal thyroid epithelium, the apoptosis-blocking gene bcl-X and the apoptosis-inducing gene bax are frequently expressed in thyroid carcinomas derived from the follicular cells. Thus, alterations in the expression of these bcl-2 family genes may contribute to the pathogenesis of thyroid carcinomas.
J Clin Endocrinol Metab 1996 Jul
PMID:Expression of the cell death-inducing gene bax in carcinomas developed from the follicular cells of the thyroid gland. 867 2

Activation-induced apoptosis is a primary mechanism for downmodulation of an immune response leading to immune homeostasis and deletion of T cells with specificities which may be harmful. These include deletion of T cells with self-specificities (autospecific) and excessively high affinity for foreign antigen which may lead to an excessively heightened immune response and septic shock. Surface molecules involved in activation-induced apoptosis involve Fas and Fas ligand (FasL), as well as the T-cell receptor (TCR) which modulates the expression and function of these molecules. Fas signaling mechanisms include the hematopoietic cell phosphatase (HCP) and sphingomyelinase, while TCR-signaling mechanisms include Nur77 and fyn kinase and unknown molecules that modulate expression of FasL. Apoptosis signals are further modulated by inhibitors or inducers of apoptosis including Bcl-2, p53, and interleukin-1 beta converting enzyme (ICE). Further understanding of the interaction of these molecules in autoimmune disease may lead to more specific therapies for immunosuppression tailored to the genetic or environmentally induced, activation-induced apoptosis defect in patients.
Clin Immunol Immunopathol 1996 Sep
PMID:The role of programmed cell death as an emerging new concept for the pathogenesis of autoimmune diseases. 881 Oct 58


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