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Biomedical subjects

H Sakagami

Publications and source records attributed to H Sakagami.

At least 163 records · Page 9Linked to original sources
PubMed1984

Prevention of phorbol ester receptor down modulation in human myeloblastic leukemia ML-1 cells by differentiation-stimulating serum components.

The phorbol esters 12-O-tetradecanoylphorbol-13-acetate, phorbol 12,13-didecanoate, phorbol 12,13-dibutyrate (PDB), and phorbol 12,13-dibenzoate were found to compete with [20-3H]-PDB binding to human myeloblastic leukemia ML-1 cells in approximate proportion to their differentiation-inducing capacity. Fetal bovine serum decreased the down modulation of phorbol ester receptor sites on these cells and increased PDB-induced differentiation. These two activities coeluted upon chromatography of fetal bovine serum on a Sephadex G-150 column. A partially purified fraction from pokeweed mitogen-stimulated human leukocyte-conditioned medium which effectively induced ML-1 cell differentiation also prevented the down modulation of PDB receptors. As indicated by Scatchard analysis, prevention of down modulation was due to stabilization of the number of binding sites rather than to a change in receptor affinity. In view of the previously observed modulation of growth factor binding by phorbol esters, the currently described alteration of phorbol ester receptor activity by differentiation-inducing factors implies an interaction between growth and differentiation factors in receptor modulation.

Animals↗
PubMed1984

Changes in histone H1 composition during differentiation of mouse myeloid leukemia cells.

The possible change due to dexamethasone treatment in the relative amounts of two major subtypes of H1 histone, H1A and H1B, in mouse myeloid leukemia cells (M1 cells) during differentiation was examined. The relative amount of H1B decreased after dexamethasone treatment and reached about one-tenth that of H1A at the fully differentiated stage. These results contrast with the results reported for normal fibroblast cells and their neoplastic counterparts. Additional findings are that phosphorylation of H1 occurs almost exclusively in the H1B subtype and fluctuates following dexamethasone treatment.

Animals↗
PubMed1984

Macromolecular and cell cycle effects of different classes of agents inducing the maturation of human myeloblastic leukemia (ML-1) cells.

The effect of various classes of differentiation-inducing agents on macromolecular synthesis was studied in a human myeloblastic leukemia cell line (ML-1). Antineoplastic drugs such as 1-beta-D-arabinofuranosylcytosine, daunorubicin, and actinomycin D caused early inhibition of DNA synthesis, which generally preceded the accrual of differentiation markers. In contrast, retinoic acid and conditioned medium from mitogen-stimulated leukocytes caused a delayed decline in DNA synthesis, which accompanied the appearance of maturing morphology. With 12-O-tetradecanoylphorbol-13-acetate, the decline in DNA synthesis was temporally linked to the onset of maturation, and this agent evidenced some properties of both the antineoplastic agents and the more physiological inducers, retinoic acid and conditioned medium. Antineoplastic agents and conditioned medium, when applied simultaneously, induced differentiation in an additive or synergistic manner, simulating the effects of 12-O-tetradecanoylphorbol-13-acetate. RNA and protein synthesis continued during maturation induced with all these agents, although a partial reduction in RNA synthesis was observed at later time points (greater than or equal to 24 hr). Agents incapable of inducing differentiation, such as cordycepin and cycloheximide, were characterized by a lack of sustained inhibition of DNA synthesis and/or by early (3 hr) inhibition of RNA or protein synthesis. The decline in DNA synthesis caused by the inducing agents was accompanied by decreased cell cycle progression, cells accumulating largely in G1 phase. With daunorubicin and actinomycin D, block of the G1-S transition was evident at 24 hr, whereas with conditioned medium and retinoic acid, accumulation in G1 occurred in a progressive fashion, greater than 77% of cells residing in this phase on Day 6. Maximal inducing doses of 12-O-tetradecanoylphorbol-13-acetate (greater than 80% differentiation) caused an accumulation of cells in G1, as well as an accumulation of cells with a G2-M-phase DNA content (approximately 40%). These observations indicate that early inhibition of DNA synthesis, with sparing of RNA and protein synthesis, is characteristic of the differentiation-inducing antineoplastic drugs examined. These agents may induce differentiation by inhibition of the proliferation path, whereas conditioned medium and retinoic acid may act by the stimulation of differentiation paths. Differentiation can be enhanced by the simultaneous application of agents targeting both of these paths.

Cell Cycle↗
PubMed1983

DNA synthesizing activity during induced differentiation in mouse myeloid leukemia (M1) cells.

Mouse myeloid leukemia (M1) cells were induced to differentiate in vitro by treatment with dexamethasone. After 8 h of treatment, induction of phagocytic and lysozymic activities and depression of DNA synthesis started at the same time and proceeded irreversibly. DNA synthesis in the nuclear system reflected primarily DNA replication rather than repair and this activity declined during M1 cell differentiation.

Animals↗
PubMed1982

Effect of growth stage on histone H1 metabolism in human diploid fibroblasts.

Metabolism of histone H1 at different stages of cell growth was investigated in order to get a better understanding of the role of histone H1 in the cell growth of human diploid fibroblasts. Histone H1 content exhibited some fluctuation during the culture stage of cell growth. When cells entered confluent phase, the ratio of histone H1 to total histones decreased significantly. Histone H1 had a turnover half-life of 80 hours whereas nucleosomal histones did not significantly turn-over regardless of the growth stage. DNA synthesis was drastically diminished with increased cell density whereas histone synthesis was less sensitive to contact-inhibition. The gradual decline of histone H1 content with increased cell density suggests that its degradation is slightly superior to its residual synthesis. When the confluent cells were seeded at low density, cell proliferation resumed and histone H1 was synthesized and deposited to chromatin in a greater amount than nucleosomal histones, thus resulting in an abrupt increase of histone H1 content. The possible role of histone H1 metabolism in normal cells is discussed.

Cell Division↗
PubMed1982

Conservation of chromosomal high mobility group proteins HMG1 and HMG2 during differentiation of mouse myeloid leukemia cells.

The possible change in the levels of high mobility group proteins HMG1, HMG2 and histone H1 and H1(0) was investigated during mouse myeloid leukemia (M1) cell differentiation. In contrast to Friend erythroleukemia cells, no change occurred in the levels of any of these proteins. However, histone H1 phosphorylation significantly decreased. The results suggest that the loss of HMG1 and HMG2 proteins is not a generalized marker for cell differentiation.

Animals↗
PubMed1981

Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3.

Mouse myeloid leukemia cells can be induced to differentiate into macrophages in vitro by 1 alpha,25-dihydroxyvitamin D3, the active form of vitamin D3. The minimal concentration of 1 alpha,25-dihydroxyvitamin D3 to induce the cell differentiation was 0.12 nM. The degree of cell differentiation in various markers induced by 12 nM 1 alpha,25-dihydroxyvitamin D3 was nearly equivalent to that induced by 1 microM dexamethasone, the most potent known stimulator. Among several markers of the differentiation by 1 alpha,25-dihydroxyvitamin D3, phagocytic activity was induced within 24 hr, and this was followed by induction of lysozyme and locomotive activities. Similar changes were also induced by 0.01-1 microM 1 alpha-hydroxyvitamin D3. 25-Hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 showed only weak inducing activity. These results suggest the possibility that, in addition to its wellknown biological activities in enhancing intestinal calcium transport and bone mineral mobilization, 1 alpha, 25-dihydroxyvitamin D3 is involved in the differentiation of bone marrow cells.

Animals↗
PubMed1981

Effect of DL-alpha-tocopherol (vitamin E) on the differentiation of mouse myeloid leukemia cell.

The effect of DL-alpha-tocopherol on the differentiation of the mouse myeloid leukemia cell line (M1) was investigated using fluorometry. The reliability of the fluorometric determination was verified by the mutual overlapping of the curves of disappearance of the radioactivity recovered as alpha-tocopherol and the loss of its fluorescence. alpha-Tocopherol solubilized into the culture medium was relatively stable (t1/2 = 147-168 hr). In corporation of alpha-tocopherol into M1 cells was time- and dose-dependent. Proliferation of M1 cells was never inhibited, but was slightly enhanced by treatment with alpha-tocopherol. alpha-Tocopherol caused a twofold increase in acid-phosphatase activity and slightly inhibited both the spontaneous- and dexamethasone-induced differentiation with respect to adhesion on glass and cell surface-rosette formation. alpha-Tocopherol also induced morphological change, making the shape of M1 cells rounder.

Animals↗