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

The mechanisms of luteal regression and rescue in women are unknown but forms of programmed cell death may be involved. The proto-oncogene bcl-2 is an important inhibitor of apoptosis but has not previously been described in the human corpus luteum. Immunohistochemical localization of bcl-2 protein was investigated in human corpora lutea obtained from women undergoing surgery during endocrine monitored menstrual cycles as well as from women who had been treated with human chorionic gonadotrophin (HCG) to prolong the luteal phase. Bcl-2 was found to be localized in granulosa-lutein, theca-lutein (as identified by co-localization of P450(17)alpha-hydroxylase) and the endothelial cells around some blood vessels. Immunoblotting demonstrated the presence of a single band of approximately MW 26 kDa. There was no apparent change in either the intensity of immunostaining or the histological localization during the normal luteal phase or following treatment with human chorionic gonadotrophin. The product of the proto-oncogene bcl-2 is present in the human corpus luteum. It is unlikely that bcl-2 expression alone is responsible for prolongation of the lifespan of the corpus luteum in early pregnancy although it is possible that the action of the bcl-2 gene present is modified by changes in other members of the bcl-2 family.
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PMID:Immunolocalization of bcl-2 in the human corpus luteum. 759 40

Apoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus (VZV), a human herpesvirus, is characterized by nuclear fragmentation of DNA into oligonucleosomal fragments and by chromatin condensation. In vitro, VZV-induced cell death is actually mediated by apoptosis. The mechanisms developed by cells to protect themselves against apoptosis could be one of the parameters allowing the establishment of virus latency. In the case of VZV, which can remain latent in sensory ganglia, we have not yet identified a cellular or viral protein which could play this protective role, since the observed apoptosis mechanism seems to be independent from Bcl-2, the most frequently described inhibitor of apoptosis.
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PMID:Varicella-zoster virus induces apoptosis in cell culture. 759 98

Hypersensitivity to cross-linking agents such as mitomycin C (MMC) is characteristic of cells from patients suffering from the inherited bone marrow failure syndrome. Fanconi anemia (FA). Here, we link MMC hypersensitivity of Epstein-Barr virus (EBV)-immortalized FA lymphoblasts to a high susceptibility for apoptosis and p53 activation. In MMC-treated FA cells belonging to complementation group C (FA-C), apoptosis followed cell cycle arrest in the G2 phase. In stably transfected FA-C cells, plasmid-driven expression of the wild-type cytoplasmic FAC protein relieved MMC-dependent G2 arrest and suppressed p53 activation. However, in both FA and non-FA lymphoblasts, p53 seemed not to be instrumental in the induction of MMC-dependent apoptosis, since overexpression of a dominant-negative p53 mutant failed to affect cell survival. In addition, no differences in the level of Bcl-2 expression, an inhibitor of apoptosis, were detected between FA and non-FA cells either in the absence or presence of MMC. Our findings suggest that FAC and the other putative FA gene products may function in a yet to be identified p53-independent apoptosis pathway.
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PMID:Fanconi anemia genes act to suppress a cross-linker-inducible p53-independent apoptosis pathway in lymphoblastoid cell lines. 856 65

The induction of tumor cell differentiation represents an attractive strategy for the treatment of a wide range of malignancies. Differentiation of HL-60 promyelocytic leukemia cells towards neutrophils or monocytes has been shown to induce apoptotic cell death, which is inhibited by bcl-2 over-expression. However, the role of the bcl-2 gene family during erythroid differentiation of human leukemia cells remains unknown. We found that human erythroleukemia (HEL) and K562, two leukemia cell lines that undergo erythroid differentiation do not express Bcl-2, but express Bcl-XL, a related protein that functions as an inhibitor of apoptosis. Differentiation of HEL or K562 cells with inducers of erythroid differentiation (hemin, retinoic acid, or transforming growth factor-beta) was accompanied by progressive cell death and degradation of genomic DNA into oligonucleosomal fragments. The loss of cellular viability was associated with downregulation of bcl-xL mRNA and protein. In contrast, the levels of Bax, another Bcl-2 family member implicated in apoptosis remained unaltered. Constitutive expression of Bcl-XL by gene transfer inhibited apoptosis triggered by erythroid differentiation of HEL K562 cells. Yet, Bcl-XL did not alter the expression of epsilon-globin, which is induced during erythoid differentiation of HEL and K562 cells, arguing that apoptosis and differentiation can be uncoupled by Bcl-XL. These results indicate that Bcl-XL acts as an antiapoptosis protein in leukemia cells that undergo erythroid differentiation and that downregulation of bcl-x is a component of the apoptotic response that is coupled to differentiation in human leukemia cells.
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PMID:Apoptosis induced by erythroid differentiation of human leukemia cell lines is inhibited by Bcl-XL. 861 10

We have evaluated by in situ nick-end labeling the presence of apoptotic cells in the spinal cord of rats with compression injury at the level of Th8-9 of mild, moderate, and severe degrees resulting in no neurologic deficit, reversible paraparesis, and paraplegia, respectively. Rats with compression injury surviving 4 or 9 days showed apoptotic glial cells in the longitudinal tracts of the Th8-9, the cranial Th7, and the caudal Th10 segments. The apoptotic cells were most frequently observed in Th7. They did not express glial fibrillar acidic protein (GFAP) and their morphology was compatible with that of oligodendrocytes. Neurons of the gray matter did not present signs of apoptosis. In addition, we studied the immunohistochemical expression of Bcl-2, an endogenous inhibitor of apoptosis. Compression induced Bcl-2 immunoreactivity in axons of the long tracts, particularly after moderate and severe compression and 1-day survival. Neurons of dorsal root ganglia were immunoreactive but the neurons of the spinal cord were unstained. The accumulation, presumably caused by arrested axonal transport in sensory pathways, was absent in rats surviving 9 days. In conclusion, compression trauma to rat spinal cord induces signs of apoptosis in glial cells, presumably oligodendrocytes of the long tracts. This may induce delayed myelin degeneration after trauma to the spinal cord. Bcl-2 does not seem to be upregulated in oligodendrocytes.
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PMID:Apoptosis and expression of Bcl-2 after compression trauma to rat spinal cord. 878 86

Bcl-2 belongs to a family of apoptosis-regulatory proteins which incorporate into the outer mitochondrial as well as nuclear membranes. The mechanism by which the proto-oncogene product Bcl-2 inhibits apoptosis is thus far elusive. We and others have shown previously that the first biochemical alteration detectable in cells undergoing apoptosis, well before nuclear changes become manifest, is a collapse of the mitochondrial inner membrane potential (delta psi m), suggesting the involvement of mitochondrial products in the apoptotic cascade. Here we show that mitochondria contain a pre-formed approximately 50-kD protein which is released upon delta psi m disruption and which, in a cell-free in vitro system, causes isolated nuclei to undergo apoptotic changes such as chromatin condensation and internucleosomal DNA fragmentation. This apoptosis-inducing factor (AIF) is blocked by N-benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (Z-VAD.fmk), an antagonist of interleukin-1 beta-converting enzyme (ICE)-like proteases that is also an efficient inhibitor of apoptosis in cells. We have tested the effect of Bcl-2 on the formation, release, and action of AIF. When preventing mitochondrial permeability transition (which accounts for the pre-apoptotic delta psi m disruption in cells), Bcl-2 hyperexpressed in the outer mitochondrial membrane also impedes the release of AIF from isolated mitochondria in vitro. In contrast, Bcl-2 does not affect the formation of AIF, which is contained in comparable quantities in control mitochondria and in mitochondria from Bcl-2-hyperexpressing cells. Furthermore, the presence of Bcl-2 in the nuclear membrane does not interfere with the action of AIF on the nucleus, nor does Bcl-2 hyperexpression protect cells against AIF. It thus appears that Bcl-2 prevents apoptosis by favoring the retention of an apoptogenic protease in mitochondria.
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PMID:Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. 887 5

Apoptosis or programmed cell death represents a mechanism by which tumor cells with DNA damage can be deleted. Bcl-2 and p53 gene products have both been linked to apoptosis. Bcl-2 plays a role as an inhibitor of apoptosis that may extend the viability of cells containing genetic alterations and facilitate tumor progression. Mutant p53 has a similar effect. The purpose of this study was to investigate the relationship between bcl-2 and p53 expression and to clarify their roles in apoptosis in different histological graded breast carcinomas. We analysed 101 invasive ductal carcinomas of the breast for the expression of bcl-2, p53, c-erbB-2, estrogen and progesterone receptors using immunohistochemistry. Reciprocal expression of bcl-2 and p53 was present in 71.3% of cases. The bcl-2+/p53-expression pattern was prevalent in histological grade I and II tumors (77.4% and 59.3% respectively) and rarely present in histological grade III (6.3%). Conversely, bcl-2-/p53+ expression pattern was rarely present in histological grade I and II tumors (3.2% and 11.1% respectively) and prevalent in histological grade III (50.0%). Our results also showed that Bcl-2 expression was positively correlated with ER and PR, more prevalent in pre-menopausal status, and negatively correlated with cerbB-2 expression. Bcl-2 expression was involved in tumor progression in well-differentiated tumors and mutant p53 could substitute for bcl-2 function in poorly differentiated tumors. The bcl-2/p53 expression pattern of tumors may be of value in predicting therapeutic response and prognosis. Bcl-2 expression was correlated with other well-established prognostic factors and bcl-2 could be an estrogen-related protein.
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PMID:Reciprocal expression of Bcl-2 and p53 in breast ductal carcinoma. 891 21

Attempts to rescue retinal ganglion cells from retrograde degeneration have had limited success, and the residual function of surviving neurons is not known. Recently, it has been found that axotomized retinal ganglion cells die by apoptotic mechanisms. We have used adult transgenic mice overexpressing the Bcl-2 protein, a powerful inhibitor of apoptosis, as a model for preventing injury-induced cell death in vivo. Several months after axotomy, the majority of retinal ganglion cells survived and exhibited normal visual responses. In control wild-type mice, the vast majority of axotomized retinal ganglion cells degenerated, and the physiological responses were abolished. These results suggest that strategies aimed at increasing Bcl-2 expression, or mimicking its function, might effectively counteract trauma-induced cell death in the central nervous system. Neuronal survival is a necessary condition in the challenge for promoting regeneration and eventually restoring neuronal function.
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PMID:The visual response of retinal ganglion cells is not altered by optic nerve transection in transgenic mice overexpressing Bcl-2. 896 63

Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes. Despite their physiological importance, the biochemical function of Bcl-2-related proteins has remained elusive. The three-dimensional structure of Bcl-xL, an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins. A key feature of these pore-forming domains is the ability to form ion channels in biological membranes. Here we demonstrate that Bcl-xL shares this functional feature. Like the bacterial toxins, Bcl-xL can insert into either synthetic lipid vesicles or planar lipid bilayers and form an ion-conducting channel. This channel is pH-sensitive and becomes cation-selective at physiological pH. The ion-conducting channel(s) formed by Bcl-xL display multiple conductance states that have identical ion selectivity. Together, these data suggest that Bcl-xL may maintain cell survival by regulating the permeability of the intracellular membranes to which it is distributed.
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PMID:Bcl-x(L) forms an ion channel in synthetic lipid membranes. 900 22

Recent studies have identified a number of cell death pathway components. In this study, we describe the role that two such components, Bik and Bak, play in initiating the apoptotic program. These Bcl-2 family members engage the death pathway downstream of the block imposed by the serpin CrmA, but upstream of the block initiated by cellular inhibitors of apoptosis, which are a family of molecules characterized by a conserved baculovirus inhibitor of apoptosis repeat motif. Distal death pathway components activated by Bik and Bak are similar to those activated by the CD-95 (Fas/Apo1) and tumor necrosis factor death receptors.
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PMID:Bik and Bak induce apoptosis downstream of CrmA but upstream of inhibitor of apoptosis. 908 97


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