Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferation of a murine macrophage cell line (BAC1.2F5) in response to colony-stimulating factor 1 (CSF-1) is inhibited by prostaglandin E2 (PGE2)-mediated elevation of intracellular cyclic AMP (cAMP). When BAC1.2F5 cells were growth arrested in early G1 by CSF-1 starvation and stimulated to synchronously enter the cell cycle by readdition of growth factor, PGE2 inhibited [3H]thymidine incorporation when added before mid-G1, but its addition at later times did not block the onset of S phase. Reversible cell cycle arrest mediated by a cAMP analog required the presence of CSF-1 for cells to initiate DNA synthesis, whereas cells released from an aphidicolin block at the G1/S boundary entered S phase in the absence of CSF-1. PGE2 or cAMP analogs did not block the initial induction of c-myc mRNA by CSF-1 but abolished the CSF-1-dependent expression of c-myc mRNA in the mid-G1 stage of the cell cycle. The cAMP-mediated reduction in c-myc RNA levels was due to decreased c-myc transcription. However, CSF-1-dependent BAC1.2F5 clones infected with a c-myc retrovirus were growth arrested by cAMP analogs despite constitutive c-myc expression. Therefore, the reduction of endogenous c-myc expression by cAMP is neither necessary nor sufficient for growth inhibition.
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PMID:Macrophage growth arrest by cyclic AMP defines a distinct checkpoint in the mid-G1 stage of the cell cycle and overrides constitutive c-myc expression. 137 14

The cloned, SV40-immortalized mouse macrophage cell line, BAC1.2F5, resembles primary macrophages in its dependence on colony-stimulating factor-1 (CSF-1) for both viability and proliferation. Re-addition of CSF-1 stimulates rapid, transient behavioural changes in starved cells, which are rounded, with diffusely organized F-actin and few intracellular vesicles. Within 1 min, cells begin to spread, forming prominent, F-actin-rich ruffles. Small vesicles (0.5-1.0 microns), formed throughout extending lamellar processes, move centripetally and, after 3-5 min, fuse to form larger vesicles (2.0-4.0 microns), clustered around the nucleus. Immunofluorescence demonstrates that CSF-1, bound to cell-surface receptors, is internalized via these vesicles. Cell spreading and ruffling peak about 5 min after restimulation. Interference reflection microscopy indicates no corresponding change in the mode of cell-substratum adhesion: a single area of close adhesion underlies most of the cell and simply broadens during spreading. Analysis of cell aggregation kinetics shows no effect of CSF-1 on intercellular adhesiveness. Measurement of cell areas after starvation and restimulation demonstrates quantitatively the time-course and concentration-dependence of cell spreading. Mean area doubles within 5 min and, after a transient peak, decreases within 30 min to the value measured before starvation. This time-course corresponds to that of CSF-1 internalization and of the phosphorylation and subsequent degradation of CSF-1 receptors. The concentration-dependence of the spreading response resembles that of CSF-1-dependent survival and proliferation. The minimum detectable stimulation of spreading occurs at the concentration (22 pM) that supports survival without proliferation. Increasing stimulation of spreading occurs over the range of concentrations that elicit increasing proliferation.
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PMID:Colony-stimulating factor-1 induces rapid behavioural responses in the mouse macrophage cell line, BAC1.2F5. 253 50