Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the apoptosis-associated proteins Bcl-2 and Bax was quantitated by flow cytometry (FCM) in chemosensitive testicular germ-cell tumor NT2 cells, and the results were compared with those obtained by Western blotting. NT2 cells were incubated with cisplatin (3.1 microM for 2 h at 37 degrees C), and 24, 48, and 72 h later were analyzed for induction of apoptosis, and for modulation of the expression of cell death suppressing protein Bcl-2, as well as cell death promoting protein Bax. Apoptosis was quantitated by binding of annexin V conjugated with fluorescein isothiocyanate (FITC) to the cell membrane. Cisplatin-treatment induced apoptosis in NT2 cells. The apoptotic cell population increased in time, and at t = 72 h after drug incubation, about 90% of cells that were present in the cell culture were apoptotic. Subsequently, we determined the expression of the Bcl-2 and Bax proteins by FCM and Western blotting before and after drug treatment. NT2 cells had low constitutive expression levels of Bcl-2 and elevated constitutive expression levels of Bax protein, as determined by both methods. At t = 24 h and 48 h after drug treatment, no changes were observed in the expression of the Bcl-2 protein, as quantitated by FCM and Western blotting. Also, the expression of the Bax protein had not changed, based on Western blotting. However, FCM revealed that in a specific subpopulation of drug-treated NT2 cells, Bax expression was increased. On the basis of forward and perpendicular light-scatter this subpopulation, which consisted of large, early apoptotic, swollen cells with increased internal complexity, was sorted, and showed abundant Bax protein by FCM and Western blotting. Our results demonstrate that the chemosensitivity of NT2 cells is probably due to a low intrinsic threshold for drug-induced apoptosis that is accompanied by overexpression of the death-promoting Bax protein during the early stages of the apoptotic process. We conclude that FCM is superior to Western blotting for the detection of heterogeneous expression of Bax in a given cell population.
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PMID:Bax upregulation is an early event in cisplatin-induced apoptosis in human testicular germ-cell tumor cell line NT2, as quantitated by flow cytometry. 904 Nov 17

The bcl-2 gene is overexpressed in the absence of gene rearrangements in most cases of B-cell chronic lymphocytic leukaemia (B-CLL) and the proto-oncogene product Bcl-2 has been shown to be a regulator of apoptosis. The activity of this protein is opposed by Bax, a homologous protein that accelerates the rate of cell death. B-lymphocyte Bcl-2 and Bax protein levels were found to be significantly altered in B-CLL and increased Bcl-2/Bax ratios were observed in both the treated and untreated patients compared with those of normal controls. These alterations were particularly pronounced in those treated patients found to be clinically unresponsive to chemotherapy. In order to determine whether Bcl-2/Bax ratios affected cell survival via an anti-apoptotic mechanism, cell death was induced in B-CLL cells in vitro using chlorambucil, and apoptosis was monitored by Annexin V and propidium iodide staining. Confirmation that the labelled cells were apoptotic was achieved by morphological assessment of cytospin preparations of cell-sorted populations. Drug-induced apoptosis in B-CLL cells was inversely related to Bcl-2/Bax ratios.
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PMID:Bcl-2/Bax ratios in chronic lymphocytic leukaemia and their correlation with in vitro apoptosis and clinical resistance. 971 44

We investigated the relationship between drug resistance and Bcl-2/Bax in B-cell chronic lymphocytic leukaemia (B-CLL). Apoptosis was induced in vitro with chlorambucil and cell death was monitored by dual-labelled FACS analysis using Annexin V and propidium iodide. Bcl-2 and Bax protein expression was quantified using FACS and a correlation between drug-induced apoptosis and Bcl-2/Bax was established. Cells were then sorted into viable and nonviable populations according to their forward and side-scatter characteristics and re-analysed for Bcl-2/Bax. The most resistant cells had elevated Bcl-2 levels and low Bax expression. Furthermore, those cells which were undergoing apoptosis showed only a marginal reduction in Bcl-2 expression, but significantly elevated Bax expression following exposure to chlorambucil. The Bcl-2/Bax was significantly greater in the cell fractions resistant to chlorambucil-induced apoptosis. This observation further supports the suggestion that Bax is the pivotal protein in determining the fate of cells following apoptotic signals.
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PMID:Elevated Bcl-2/Bax are a consistent feature of apoptosis resistance in B-cell chronic lymphocytic leukaemia and are correlated with in vivo chemoresistance. 951 6

Bax and Bcl-2 are a pair of important genes that control programmed cell death, or apoptosis, with Bax being the apoptosis promoter and Bcl-2 the apoptosis protector. Although the detailed mechanism is unknown, the protein products of these two genes form protein dimers with each other and the relative ratio of the two proteins is believed to be a determinant of the balance between life and death. In our preliminary study, we found that K562 erythroleukemia cells have an extremely low level of endogenous Bcl-2 expression and a fairly high level of endogenous Bax expression. We constructed Bax and Bcl-2 expression vectors and transfected them into K562 cells. We found that transfection of Bax vector increased the expression of Bax protein; a shortened form of Bax also appeared. Cell death analysis using the Annexin V assay showed that the Bax vector caused significantly more apoptotic cells that the Bcl-2 or pCI-neo vector did. After selection with G418, Bax, Bcl-2 and pCI-neo stably transfected cells were established. These three cell lines were examined for their response to the chemotherapeutic agents ara-C, doxorubicin, etoposide and SN-38. Bax-K562 cells showed significantly higher fractions of apoptotic cells than pCI-neo-K562 cells when treated with ara-C, doxorubicin or SN-38. No sensitization effect was seen when etoposide was used. In contrast, Bcl-2-K562 cells had fewer apoptotic cells than pCI-neo-K562 cells after treatment with all these agents. Therefore, Bax may sensitize K562 cells to apoptosis induced by a wide range of, but not all, chemotherapeutic agents.
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PMID:Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis induced by selective chemotherapeutic agents. 956 26

Endostatin, a carboxyl-terminal fragment of collagen XVIII, has been shown to regress tumors in mice. In this study, we have analyzed the mechanism of endostatin action on endothelial cells and nonendothelial cells. Endostatin treatment of cow pulmonary artery endothelial cells caused apoptosis, as demonstrated by three methods, annexin V-fluorescein isothiocyanate staining, caspase 3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling assay. Moreover, addition of endostatin led to a marked reduction of the Bcl-2 and Bcl-XL anti-apoptotic protein, whereas Bax protein levels were unaffected. These effects were not seen in several nonendothelial cells. Collectively, these findings provide important mechanistic insight into endostatin action.
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PMID:Endostatin induces endothelial cell apoptosis. 1020 87

HeLa X human skin fibroblast hybrid cells have been developed into a model for radiation-induced neoplastic transformation of human cells. Previous studies indicate that the appearance of neoplastically transformed foci in this system is delayed for several population doublings after irradiation and appears to involve the loss of putative tumor suppressor loci on fibroblast chromosomes 11 and 14. We now show that after treatment with 7 Gy of X-rays, transformed foci initiation correlates with delayed apoptosis initiated in the progeny of the irradiated cells after 10-12 cell divisions and with reduced plating efficiency (delayed death). The cells develop classic apoptotic morphology, positive terminal deoxynucleotidyl transferase-mediated nick end labeling and phosphatidylserine (annexin V) staining, and cleavage of poly(ADP-ribose) polymerase. In addition, a delayed induction of the p53 protein and the proapoptotic Bax protein is evident over a week after radiation exposure. We propose that a delayed build-up of mitosis-dependent genomic DNA damage or a loss of genetic material over time (10-12 cell divisions postirradiation) has two relevant outcomes: (a) cell death due to the delayed induction of a p53-dependent apoptosis; and (b) neoplastic transformation of a minor subset of survivors that has lost fibroblast chromosomes 11 and 14 (tumor suppressor loci for this system) and has either evaded apoptosis or not acquired enough genetic damage to induce apoptosis. It is postulated that both phenomena result from X-ray-induced, translesion-mediated genomic instability.
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PMID:Delayed apoptotic responses associated with radiation-induced neoplastic transformation of human hybrid cells. 1046 94

EB1089, a novel 1,25-dihydroxyvitamin D3 analogue, has been known to have potent antiproliferative properties in a variety of malignant cells both in vitro and in vivo. In the present study, we analysed the effect of EB1089 on NCI-H929 human myeloma cells. EB1089 inhibited cell growth of NCI-H929 and efficiently induced the G1 phase arrest of the cell cycle in a dose-dependent manner. We could also detect apoptosis in NCI-H929 cells exposed to EB1089 (1 x 10-7 M for 72 h) using the sub-G1 group of the cell cycle by FACS and annexin V binding assays. Induction of apoptosis by EB1089 was associated with down-regulation of the Bcl-2 protein without change of the Bax protein. Regarding caspase activity, which plays a crucial role in apoptosis, EB1089-treated NCI-H929 cells revealed an increased activity of caspase 3 protease accompanied by degradation of the PARP protein in a dose- and time-dependent manner. In addition, EB1089 caused the down-regulation of p44 extracellular signal-related kinase (ERK) activity and up-regulation of the p38 kinase activity during apoptosis of NCI-H929 cells. These results suggest that EB1089 inhibits growth of NCI-H929 cells via G1 cell cycle arrest as well as apoptosis by activating p38 kinase and suppressing ERK activity.
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PMID:Induction of apoptosis by vitamin D3 analogue EB1089 in NCI-H929 myeloma cells via activation of caspase 3 and p38 MAP kinase. 1088 7

In the present study, we investigated the in vitro apoptotic response of leukemic cells to the cellular stress induced by homoharringtonine (HHT), a plant alkaloid with antileukemic activity which is currently being tested for treatment of acute and chronic leukemias. A comparison of leukemic cell lines with different p53 gene status revealed a considerably higher sensitivity to HHT-induced apoptosis in the cells with a wt p53, and apoptotic events in wt p53 leukemia cells (MOLT-3 cell line) were studied in more detail. To this end, we examined components of apoptotic cascades including Bax expression and its intracellular localization, changes of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) levels, cytochrome c release from mitochondria and activation of caspases. Bax protein levels did not increase despite an up-regulation of bax at mRNA level. However, Bax translocation from cytosol towards mitochondria was observed. In addition, we observed a release of cytochrome c from the mitochondria, and the localization changes of both Bax and cytochrome c were found already at the early, annexin V-negative stage of HHT-induced apoptosis. HHT-treated MOLT-3 cells revealed loss of MMP as well as activation of caspases demonstrated by DEVD-, IETD- and LEHD-tetrapeptide cleavage activity in the cell lysates. ROS levels only slightly increased in HHT-treated cells and antioxidants did not prevent apoptosis and MMP changes. Therefore, wt p53 leukemic cells respond to HHT-specific cellular stress by induction of ROS-independent apoptotic pathway characterized by translocation of Bax, mitochondrial cytochrome c release and activation of caspases.
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PMID:Apoptotic response to homoharringtonine in human wt p53 leukemic cells is independent of reactive oxygen species generation and implicates Bax translocation, mitochondrial cytochrome c release and caspase activation. 1136 58

It has been shown that the novel synthetic triterpenoid CDDO inhibits proliferation and induces differentiation and apoptosis in myeloid leukemia cells. In the current study the effects of the C-28 methyl ester of CDDO, CDDO-Me, were analyzed on cell growth and apoptosis of leukemic cell lines and primary acute myelogenous leukemia (AML). CDDO-Me decreased the viability of leukemic cell lines, including multidrug resistant (MDR)-1-overexpressing, p53(null) HL-60-Dox and of primary AML cells, and it was 3- to 5-fold more active than CDDO. CDDO-Me induced a loss of mitochondrial membrane potential, induction of caspase-3 cleavage, increase in annexin V binding and DNA fragmentation, suggesting the induction of apoptosis. CDDO-Me induced pro-apoptotic Bax protein that preceded caspase activation. Furthermore, CDDO-Me inhibited the activation of ERK1/2, as determined by the inhibition of mitochondrial ERK1/2 phosphorylation, and it blocked Bcl-2 phosphorylation, rendering Bcl-2 less anti-apoptotic. CDDO-Me induced granulo-monocytic differentiation in HL-60 cells and monocytic differentiation in primary cells. Of significance, colony formation of AML progenitors was significantly inhibited in a dose-dependent fashion, whereas normal CD34(+) progenitor cells were less affected. Combinations with ATRA or the RXR-specific ligand LG100268 enhanced the effects of CDDO-Me on cell viability and terminal differentiation of myeloid leukemic cell lines. In conclusion, CDDO-Me is an MDR-1- and a p53-independent compound that exerts strong antiproliferative, apoptotic, and differentiating effects in myeloid leukemic cell lines and in primary AML samples when given in submicromolar concentrations. Differential effects of CDDO-Me on leukemic and normal progenitor cells suggest that CDDO-Me has potential as a novel compound in the treatment of hematologic malignancies.
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PMID:Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia. 1175 88

We have studied the magnitude of apoptosis in heart, slow-twitch skeletal muscle (soleus) and fast-twitch skeletal muscle (gastrocnemius) of rats exposed to 3 weeks in vivo chronic hypoxia. Apoptosis was evaluated biochemically by DNA laddering and by TUNEL and annexin V-staining. The expression of Bax and Bcl-2 proteins was determined by immunohistochemistry and Western blotting. Western blot analysis revealed only a slight difference in Bax expression among the different tissues under normoxic and hypoxic conditions; therefore we can consider that Bax protein is constitutively expressed in muscle tissues. However a singular pattern of Bcl-2 expression was observed among the different tissues under normoxic conditions. Bcl-2 protein was more expressed in fast-twitch glycolytic muscles than in slow-twitch or oxidative muscles with a highest value found in gastrocnemius (4926 +/- 280 AU), followed by soleus (2138 +/- 200 AU) and a very low expression was displayed in the heart muscle (543 +/- 50 AU). After exposure to hypoxia for 21 days (10% O2), Bcl-2 protein expression markedly increased, (44%) in gastrocnemius, (323%) in soleus and (1178%) in heart, with significant differences (p < 0.05 student t-test), reaching a similar threshold of expression in both types of muscles. Furthermore, no sign of apoptosis was detected by TUNEL assay, annexin V-binding assay or DNA electrophoresis analysis. The latter suggested some indiscriminate fragmentations of DNA without apoptosis. In conclusion, we postulate that these protein modifications could represent a adaptative mechanism allowing a better protection against the lack of oxygen in oxidative muscles by preventing apoptosis.
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PMID:Bcl-2/Bax protein expression in heart, slow-twitch and fast-twitch muscles in young rats growing under chronic hypoxia conditions. 1176 44


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