scholarly journals d-myo-inositol 1,3,4,5-tetrakisphosphate releases Ca2+ from crude microsomes and enriched vesicular plasma membranes, but not from intracellular stores of permeabilized T-lymphocytes and monocytes

1992 ◽  
Vol 288 (2) ◽  
pp. 489-495 ◽  
Author(s):  
A H Guse ◽  
E Roth ◽  
F Emmrich

In the human T-lymphocyte cell lines Jurkat and HPB.ALL and the human monocytoid cell line U937, Ins(1,3,4,5)P4 triggers a dose-dependent release of Ca2+ from crude microsomal preparations, with a half-maximal effective concentration (EC50) of 1.2-2.3 microM. Similar results were obtained with enriched vesicular plasma membranes from U937 cells. However, in permeabilized preparations of the same cell types only Ins(1,4,5)P3 was able to release Ca2+ from intracellular stores, with EC50 values in the range 0.11-0.84 microM. In crude microsomes the effects of Ins(1,3,4,5)P4 and Ins(2,4,5)P3, a non-metabolizable InsP3 isomer, occurred independently of each other, indicating subpopulations of Ins(1,3,4,5)P4- and Ins(1,4,5)P3-sensitive vesicles. The Ins(1,3,4,5)P4 preparation used for the Ca(2+)-release experiments contains neither Ca2+ nor contaminating Ins(1,4,5)P3 and was not metabolized to Ins(1,4,5)P3 during the Ca(2+)-release experiments. We conclude that Ins(1,3,4,5)P4 independently of Ins(1,4,5)P3 induces a Ca2+ flux via a membrane compartment, most likely the plasma membrane, that is functionally destroyed during the permeabilization of the cells.

2013 ◽  
Vol 86 (5) ◽  
pp. 785-794 ◽  
Author(s):  
Dominik Markel ◽  
Elena Lam ◽  
Gabriele Harste ◽  
Sebastian Darr ◽  
Mirja Ramke ◽  
...  

2017 ◽  
Vol 18 (7) ◽  
pp. 1409 ◽  
Author(s):  
Man Liu ◽  
Rumana Yasmeen ◽  
Naomi Fukagawa ◽  
Liangli Yu ◽  
Young Kim ◽  
...  

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1960-1967
Author(s):  
E Elstner ◽  
YY Lee ◽  
M Hashiya ◽  
S Pakkala ◽  
L Binderup ◽  
...  

We have evaluated seven recently synthesized vitamin D3 analogs for their abilities to inhibit clonal growth of leukemic cells, to induce leukemic cell differentiation, to stimulate clonal growth of normal myeloid committed stem cells, and to transactivate a reporter gene having a 1,25(OH)2D3 response element (VDRE). The 1,25(OH)2–20-epi-D3 showed extraordinary activity; at 10(-11) mol/L it inhibited clonal growth of 87% of HL-60 myeloblast cells, 60% of S-LB1 cells (human T- cell lymphotropic virus type 1 [HTLV-1]-immortalized human T-lymphocyte cell line) and 50% of leukemic clonogenic cells (colony-forming unit- leukemia) obtained from patients with acute myelogenous leukemia. No effect of either 1,25(OH)2D3 or 1,25(OH)2–20-epi-D3 was observed on the clonal proliferation of an HTLV-1-immortalized human T-lymphocyte cell line (Ab-VDR) having nonfunctional 1,25 (OH)2D3 cellular receptors (VDR). The abilities of 1,25(OH)2–20-epi-D3 to induce differentiation of HL-60 cells, as measured by generation of superoxide and nonspecific esterase production, was less than its antiproliferative activities. This analog stimulated colony-forming unit-granulocyte-macrophage growth from normal human bone marrow. To gain insights into the remarkable antileukemic activities of 1,25(OH)2–20-epi-D3, we examined its ability to enter HL-60 cells, bind to the VDR, and interact with a transfected VDRE attached upstream of a TK promoter-driven reporter gene (chloramphenicol acetyl transferase [CAT]). The 1,25(OH)2–20-epi- D3 potently increased CAT activity (> 16-fold, as compared with cells transfected with control receptor having no VDRE); paradoxically, 1,25(OH)2–20-epi-D3 was of equal potency to 1,25(OH)2D3 in transactivating the VDRE-containing reporter gene, even though the analog had a 1,000-fold greater antileukemic effect as compared with 1,25(OH)2D3. In summary, we have identified an extremely potent 1,25(OH)2D3 analog with antiproliferative and differentiating effects on leukemic cells and that may be clinically useful. This analog appears to generate biologic responses via the classical VDR pathway, but further studies are required to elucidate the mechanism by which this analog produces its prominent activities.


Blood ◽  
1978 ◽  
Vol 52 (5) ◽  
pp. 1068-1072 ◽  
Author(s):  
DW Golde ◽  
SG Quan ◽  
MJ Cline

Abstract We derived a permanent human T lymphocyte cell line that elaborates a potent colony-stimulating activity (CSA). The line was established with spleen cells from a patient with a T lymphocyte variant of hairy-cell leukemia. These cells form rosettes with sheep erythrocytes, show a proliferative response to phytohemagglutinin, and are lysed by antithymocyte globulin. They do not synthesize immunoglobulin, nor do they contain Epstein-Barr virus. CSA is regularly detected in the supernatant medium after 3 days culture. In the presence of PHA there is augmented elaboration of CSA; maximal activity is reached by 2 days and is 20% greater than that produced by a feeder layer of 1 X 10(6) peripheral blood leukocytes. One microliter of the supernatant material stimulated colony formation from the light-density nonadherent fraction of human bone marrow; there was maximal activity between 10 and 50 microliter/ml. Conditioned medium from these cells has little effect in stimulating CFU-C from murine bone marrow. The availability of a human T lymphocyte line producing CSA will provide a source for large quantities of the lymphocyte-derived hormone and permit a definition of factors modulating the interaction of T lymphocytes with granulocyte and monocyte stem cells.


1995 ◽  
Vol 85 (1) ◽  
pp. 78-81 ◽  
Author(s):  
Keld Kaltoft ◽  
Birgit Holm Hansen ◽  
Charlotte B. Pedersen ◽  
Søren Pedersen ◽  
Kristian Thestrup-Pedersen

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