UMLS:C0023418 - FACTA Search

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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A functional study of cell surface A2b adenosine receptors was performed on the T cell leukaemia line, Jurkat. 2. A2b receptors were coupled both to the adenylate cyclase system and to intracellular calcium channels. In fact, the agonist of A2b receptors, 5'-N-ethylcarboxamidoadenosine (NECA), led to a transient accumulation of intracellular calcium by an inositol phosphate-independent mechanism. 3. The NECA-induced accumulation of cGMP was not responsible for the calcium mobilization via A2b receptors. 4. The calcium response elicited by activation of A2b receptors was independent of that evoked by activation of the T cell receptor. 5. These findings not only delineate a novel transduction mechanism for adenosine but also support a specific role for adenosine in modulating signals elicited via the T cell receptor.
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PMID:Calcium mobilization in Jurkat cells via A2b adenosine receptors. 940 72

The protein Mad1 heterodimerizes with Max to form an E-box binding complex able to interfere with the transcriptional and transforming activities of c-Myc. Downregulation of c-Myc accompanied by induction of Mad1 upon differentiation has fueled the notion that Mad1 may play a role in the cessation of proliferation associated with the differentiation process. Since studies on Mad1 expression have so far been limited to cells undergoing differentiation, it was of interest to examine Mad1 expression in a cell system unable to differentiate. To do so, we utilized the leukemia-derived B-precursor cell line, Reh, and studied the expressions of Mad1, c-Myc, Mxil, and Max during cAMP-mediated growth inhibition of these cells. Thus, the adenylate cyclase activator forskolin induced growth inhibition of the cells in the G1 phase of the cell cycle. This growth inhibition was associated with transient increased expression of Mad1 concomitant with transient downregulation of c-Myc. The Mad1 protein levels essentially paralleled those of mRNA, with peak levels at 4 h of forskolin treatment. By coimmunoprecipitation we detected increased binding of Mad1 to Max in forskolin-treated cells, indicating that the changes in Mad1 protein levels had functional implications. By continually treating Reh cells with forskolin for 72 h, we observed a sustained elevated expression of Mad1 concomitant with downregulated c-Myc expression, still without changing the differentiation profile of the Reh cells. Interestingly, we showed that other known cell cycle regulatory proteins also were transiently regulated by forskolin. To this extent, following forskolin treatment of Reh cells, cyclin E-cdk2 activity was transiently reduced concomitant with dephosphorylation of pRB. We suggest that the early changes in Mad1 and the cell cycle regulatory proteins initiate a chain of events resulting in permanent growth arrest. Thus, the increased expression of Mad1 in the absence of differentiation indicates that Mad1 expression in Reh cells is linked to growth arrest per se.
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PMID:Mad1 expression in the absence of differentiation: effect of cAMP on the B-lymphoid cell line Reh. 988 93

The effects of prostaglandin E2, forskolin, and phorbol 12-myristate 13-acetate on cell proliferation, cell surface antigen expression, vitamin D-24-hydroxylase activity and vitamin D receptor (VDR) expression have been studied in an adherent variant (Ad-HL60) of the human HL60 promyelomonocytic leukemia cell line. Ad-HL60 cells have a more differentiated phenotype than the nonadherent HL60 cells from which they were derived and, unlike the parent cell line, constitutively express vitamin D-24-hydroxylase activity. Treatment of Ad-HL60 cells with 1 microM PGE2 resulted in a decrease in the rate of cell proliferation (cell numbers were approximately 23% of control values after 72 h treatment), a change in expression of leukocyte surface antigens (decreased CD13 and CD14, increased CD11b and CD49d expression), an increase in the synthesis of 24,25-dihydroxyvitamin D3 from substrate 25-hydroxyvitamin D3 (control 5.76 +/- 0.17, 72 h PGE2-treated cells 12.10 +/- 1.90 pmol/h/10(6) cells), and an increase in receptors for the active metabolite of vitamin D, 1 alpha,25-dihydroxyvitamin D3, from 3910 to 11285 receptors per cell in control and 7-day treated cells, respectively. Prostaglandin E2 may be acting via a mechanism involving cyclic AMP in these cells, as we have also demonstrated that 10 microM forskolin, an adenylate cyclase activator, has similar effects. Phorbol 12-myristate 13-acetate had little effect on any of the parameters measured in this cell line.
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PMID:Prostaglandin E2 regulates vitamin D receptor expression, vitamin D-24-hydroxylase activity and cell proliferation in an adherent human myeloid leukemia cell line (Ad-HL60). 1041 Mar 79

The regulatory (R) subunits of cAMP-dependent protein kinase (PKA) are implicated in the regulation of cell proliferation and differentiation. There are two isoforms of PKA that are distinguished by two types of R subunit, RI and RII. Evidence suggests that RI is associated with proliferation and RII is associated with cell differentiation. Previous work in this laboratory has demonstrated that depletion of the RIalpha subunit by treatment with an antisense oligonucleotide (ODN) induces differentiation in leukemia cells and growth arrest and apoptosis in epithelial cancer cells. Using the prostate cancer cell line PC3M as a model system, we have developed a cell line that overexpresses a retroviral vector construct containing the RIalpha antisense gene. This cell line has been characterized and the effectiveness of the construct determined. In the work presented here, we demonstrate by immunocytochemistry that treatment with RIalpha antisense ODN induces translocation of the Calpha subunit of PKA to the nucleus of PC3M prostate cancer cells. The translocation of Calpha triggered by exogenous antisense ODN treatment mirrors that observed in cells endogenously overexpressing the antisense gene. Triggering the nuclear translocation of the Calpha subunit of PKA in the cell may be an important mechanism of action of RIalpha antisense that regulates cell growth independent of adenylate cyclase and cellular cAMP levels. The nuclear localization of the Calpha subunit of PKA may be an essential step in revealing the mechanism whereby this critical kinase regulates cell growth.
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PMID:Nuclear translocation of the catalytic subunit of protein kinase A induced by an antisense oligonucleotide directed against the RIalpha regulatory subunit. 1175 85

The studies on the inhibitory effect exerted by Cholera Toxin (CT) on cell growth and proliferation indicate a remarkable heterogeneity of cell response suggesting that the inhibition represents the final event of many different ways or mechanisms. After CT binding, cAMP accumulation may not occur (as in L1210 leukemia cells) or, when occurring (as in SR-4987 stromal cells), may not be coupled with the antiproliferative effect of CT. In WEHI-3B cells CT binds a Gal-GalNac-GM1b receptor and the anticlonogenic effect of CT seems correlated with cAMP accumulation. To demonstrate the central role of cAMP in WEHI-3B cells, starting from the sensitive cell strain we selected and established a clone of WEHI-3B resistant to CT. This revertant clone (WEHI-3B/CT/REV) is currently cultured in the absence of CT and in the proliferation assay shows a dramatic resistance (>46,000 than the parental cells). Stimulation ofWEHI-3B/CT/REV cells by cholera toxin failed to enhance cAMP and the ganglioside-CT binding studied on Thin Layer Chromatography (TLC) blots showed that the resistant cells lost the spot correspondent to the migration of Gal-GalNac-GM1b ganglioside. Both the lines respond at the same level to the adenylate cyclase stimulation by forskolin and the incorporation of GM1a did not decrease the resistance of WEHl-3B/CT/REV. These data confirm that Gal-GalNac-GM1b is the most important functional receptor for CT in WEHI-3B cells able to transduce the signal by enhancing cAMP which in turn inhibits cell proliferation (probably by cAMP dependent protein kinase activation). Our study describes the first cell line resistant to CT originated from a susceptible parental strain and provides a new interesting cell model for studying the cAMP dependent mechanisms involved in cell growth regulation.
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PMID:Selection of a WEHI-3B leukemia cell subclone resistant to inhibition by cholera toxin. 1208 75

The second messenger cyclic adenosine monophosphate (cAMP) plays an important role in cell proliferation, differentiation and apoptosis. In the present work, we evaluated the cAMP signaling in acute promyelocytic leukemia (APL) cells in the context of differentiation induced by all-trans retinoic acid (ATRA). There was a marked increase in the intracellular cAMP level within a few minutes after treatment with ATRA in APL cell line NB4 and fresh APL cells, whereas no such phenomenon was observed in NB4-R1 cells that are resistant to ATRA-induced maturation. In addition, the basal level of intracellular cAMP was lower in NB4-R1 than in NB4 cells. Mechanistic study showed that this induction of cAMP was mediated through the activation of adenylate cyclase. Moreover, we found that cAMP-dependent protein kinase (PKA) activity was quickly upregulated in parallel in ATRA-treated NB4 cells, and the phosphorylation of RARalpha by PKA could increase its transactivation effect. Use of H-89, an inhibitor of PKA, could partially suppress the transcriptional expression of ATRA target genes and ATRA-induced differentiation of APL cells. Taken together, we suggested a crosstalk between ATRA-induced cytosolic pathway and nuclear pathway in APL cell differentiation.
Leukemia 2004 Feb
PMID:Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation. 1462 75

Previously we identified a six-membered fragment 354TQVEHR359 of the C-terminal part of the PEDF (Pigment Epithelium-Derived Factor) differentiation factor molecule that shares homology with fragment 41TGENHR46 of the HLDF (Human Leukemia Differentiation Factor) differentiation factor molecule, which is responsible for its differentiation activity. HLDF has been isolated from the culture medium of human promyelocytic leukemia cell line HL-60. Hexapeptides HLDF-6 (TGENHR) and PEDF-6 (TQVEHR) corresponding to these HLDF and PEDF molecule fragments, which were previously shown to induce cell differentiation (Kostanyan et al. (2000) Russian Journal of Bioorganic Chemistry, 26, 505-511), also have neuroprotective properties. Both peptides prevent degeneration of Purkinje cells of rat cerebellar vermis upon chemical hypoxia induced by sodium azide in vivo; this effect is also observed on a behavioral level. Peptide HLDF-6 but not PEDF-6 promotes survival of HL-60 cells upon chemical hypoxia. Peptides HLDF-6 and PEDF-6 affect different second messenger biosynthesis systems in HL-60 cells. HLDF-6 diminishes cyclic AMP level in those cells due to adenylate cyclase inhibition, while PEDF-6 inhibits phosphatidylinositol-specific phospholipase C stimulated by aluminum tetrafluoride anions.
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PMID:Different mechanisms of protective and differentiative activities of homological peptides TGENHR and TQVEHR. 1537 65

Human T-cell leukemia virus type I (HTLV-I) transcription generally depends on the ability of the viral Tax protein to bind the CREB transcription factor and form an active complex by recruiting CBP/p300 coactivators to the long terminal repeat (LTR). Studies have demonstrated that T-cell activating agents that stimulate CREB are potent inducers of HTLV-I transcription. Herein, we demonstrate that bpV[pic], a protein tyrosine phosphatase (PTP) inhibitor activates the HTLV-I LTR in the presence and absence of Tax expression. Optimal activation occurred at 8 h and was synergistic with forskolin or PGE(2). Infected cell lines and cells transfected with HTLV-I proviral DNA were equally responsive to the synergistic effect of bpV and forskolin on HTLV-I gene expression. Activation of the LTR by bpV[pic] was T-cell receptor-independent, but required ZAP70, calcineurin activity and functional calcium entry. Inhibition of the SHP-1 PTP was suggested to be important. Transfection experiments with a CREB dominant-negative mutant and with isolated TRE1- or CREB-responsive reporter constructs and treatment with the MDL-12,330A adenylate cyclase inhibitor all supported the involvement of a CREB/ATF family member in this bpV-dependent activation of the HTLV-I LTR, although CREB itself did not seem to be involved. Analysis of HTLV-I reporter constructs containing mutated CREB-binding sites also implied the involvement of another element in this activation. These results demonstrate for the first time a powerful effect of PTP inhibitors on HTLV-I LTR activity and suggest participation of both CREB-dependent and -independent pathways in this activation.
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PMID:Activation of HTLV-I gene transcription by protein tyrosine phosphatase inhibitors. 1551 18

In this study, the expression and functional characterization of currents through the CFTR (cystic fibrosis transmembrane regulator) and ORCC (outwardly rectifying chloride channels) were determined in wild-type K562 chronic human leukemia cells (K562-WT) and in its resistant counterpart, the vincristine resistant cell line (K562-Vinc). Expression of the CFTR and MDR1 (multidrug resistant) gene products was determined by a semi-quantitative RT-PCR protocol. The amplified products in K562-WT and K562-Vinc showed two bands corresponding to CFTR and MDR1. MDR1 mRNA increased by 20-fold in K562-Vinc whereas no change in CFTR mRNA levels was observed. CFTR and ORCC channel activity were measured with a whole cell configuration of the patch clamp technique. Forskolin (40 microM n activator of adenylate cyclase, added to the extracellular side increased the current in both cell lines. A fraction of the activated whole cell currents was inhibited by 500 microM 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS) and subsequent addition of 500 microM diphenylamine-2-carboxylate (DPC plus DIDS) further inhibited the remaining currents. The levels of forskolin-activated currents and subsequent blockade were similar in both cell lines. The effect of forskolin was prevented in cells previously exposed to 500 microM DPC. The effects of DIDS and DPC on the forskolin-activated whole cell currents support the idea that both CFTR and ORCC are generating a significant fraction of these currents with DIDS inhibiting ORCC currents and DPC inhibiting CFTR currents when the blockers are added one after another to the extracellular side. Finally, we show that exposure of K562 cells to vincristine which results in the over expression of MDR1 is not accompanied by a significant down regulation of CFTR as in other cells.
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PMID:Ionic currents in multidrug resistant K562 human leukemic cells. 1603 30

Recently, we have shown that treatment of rat C6 glioma cells with the raft disruptor methyl-beta-cyclodextrin (MCD) doubles the binding of anandamide (AEA) to type-1 cannabinoid receptors (CB1R), followed by CB1R-dependent signaling via adenylate cyclase and p42/p44 MAPK activity. In the present study, we investigated whether type-2 cannabinoid receptors (CB2R), widely expressed in immune cells, also are modulated by MCD. We show that treatment of human DAUDI leukemia cells with MCD does not affect AEA binding to CB2R, and that receptor activation triggers similar [35S]guanosine-5'-O-(3-thiotriphosphate) binding in MCD-treated and control cells, similar adenylate cyclase and MAPK activity, and similar MAPK-dependent protection against apoptosis. The other AEA-binding receptor transient receptor potential channel vanilloid receptor subunit 1, the AEA synthetase N-acyl-phosphatidylethanolamine-phospholipase D, and the AEA hydrolase fatty acid amide hydrolase were not affected by MCD, whereas the AEA membrane transporter was inhibited (approximately 55%) compared with controls. Furthermore, neither diacylglycerol lipase nor monoacylglycerol lipase, which respectively synthesize and degrade 2-arachidonoylglycerol, were affected by MCD in DAUDI or C6 cells, whereas the transport of 2-arachidonoylglycerol was reduced to approximately 50%. Instead, membrane cholesterol enrichment almost doubled the uptake of AEA and 2-arachidonoylglycerol in both cell types. Finally, transfection experiments with human U937 immune cells, and the use of primary cells expressing CB1R or CB2R, ruled out that the cellular environment could account per se for the different modulation of CB receptor subtypes by MCD. In conclusion, the present data demonstrate that lipid rafts control CB1R, but not CB2R, and endocannabinoid transport in immune and neuronal cells.
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PMID:Effect of lipid rafts on Cb2 receptor signaling and 2-arachidonoyl-glycerol metabolism in human immune cells. 1701 79

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