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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyrroline 5-carboxylate, an intermediate of amino acid metabolism, is released into medium by cultured normal human fibroblasts. With cells made quiescent by serum starvation, the addition of 10% fetal bovine serum augmented the release of pyrroline 5-carboxylate into medium by 2.5-fold. Although platelet-derived growth factor was without effect, both insulin and insulinlike growth factor-1 nearly reproduced the serum effect. The dose-dependence of insulin and insulinlike growth factor 1 effects suggested their mediation by their own respective receptors. Although the mechanism for the stimulatory effect remains unknown, these effects of insulin and insulinlike growth factor 1 on pyrroline 5-carboxylate suggest hormonal regulation of pyrroline 5-carboxylate release.
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PMID:Accumulation of pyrroline 5-carboxylic acid in conditioned medium of cultured fibroblast: stimulatory effects of serum, insulin, and IGF-1. 191 83

The neu proto-oncogene product has been found to exist in two interconvertible forms in G8/DHFR mouse fibroblasts. The 185-kilodalton form (p185) present in growing cells is replaced by a 175-kilodalton form (p175) under conditions of serum starvation. This low molecular weight form accounts almost exclusively for the phosphotyrosine content of the receptor and is associated with increased tyrosine kinase activity. Addition of serum, platelet-derived growth factor or tumor promoter induces conversion of p175 to p185 within minutes, and this increase in molecular weight is associated with phosphorylation of serine and threonine; removal of serum growth factors is followed by replacement of p185 with p175 over several hours. Unlike G8/DHFR cells, the human breast cancer cell line SK-Br-3 expresses a high molecular weight neu/HER2 receptor with unchanged phosphotyrosine content in both serum-starved and serum-stimulated cultures. These findings indicate that activation of the neu proto-oncogene product in G8/DHFR cells may be regulated in part by protein kinase C-mediated receptor transmodulation rather than by ligand availability alone.
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PMID:Modulation of a Mr 175,000 c-neu receptor isoform in G8/DHFR cells by serum starvation. 197 80

To investigate whether resting cells of 3T3 mouse fibroblasts carry out de novo synthesis of deoxyribonucleoside triphosphates, we determined the turnover of the thymidine triphosphate pool of G0 cells obtained by starvation of cultures for platelet-derived growth factor. These cells were contaminated by less than 1% S-phase cells. In the absence of deoxyribonucleosides in the medium one million G0 cells contained 5 pmole of dTTP with a turnover of 0.09 pmole/min. S-phase cells in comparison contained a 20 times larger dTTP pool with a more than 200-fold faster turnover. Our results suggest that G0 cells carry out a slow but finite de novo synthesis of deoxyribonucleoside triphosphates to satisfy the cells' requirement for DNA repair and mitochondrial DNA synthesis.
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PMID:Dynamics of the thymidine triphosphate pool during the cell cycle of synchronized 3T3 mouse fibroblasts. 339 63

Kinetic analysis of cellular response to serum deprivation or inhibition of protein synthesis was performed on Swiss 3T3 cells. Time-lapse cinematographic analysis of individual cells transiently exposed to serum-free medium (with or without the addition of purified growth factors) or cycloheximide enabled a detailed mapping of the magnitude and variability of cellular response in different parts of the cell cycle. In all cells, in all stages of the cell cycle, serum deprivation resulted in inhibition of protein synthesis, but only in postmitotic cells in the first 3-4 hr of G1 (here denoted the G1pm phase) did it produce cell-cycle arrest. During G1pm, the cells are highly dependent on the continuous presence of serum growth factors and a high level of protein synthesis in order to progress toward mitosis. A 1-hr exposure to serum-free medium or to cycloheximide was sufficient to force most G1pm cells into a state of quiescence (G0), from which the cells required 8 hr to return to G1pm. During G1pm the cells complete the growth factor-dependent processes leading to commitment for proliferation. Thereafter they enter the growth factor-independent pre-DNA-synthetic part of G1 (here denoted G1ps). The commitment process in G1pm could be successfully completed in the presence of platelet-derived growth factor as the only supplied growth factor. Epidermal growth factor and insulin were insufficient for the completion of the commitment processes in G1pm, although they were able to temporarily prevent the G1pm cells from entering G0 during serum starvation. Under conditions optimal for proliferation, the cells complete the commitment processes in G1pm within a remarkably constant time period. Almost all cells in the population left G1pm and entered G1ps between the third and fourth hour after mitosis. The duration of G1ps, on the other hand, showed a large intercellular variability consistent with a transition-probability event. In fact, G1ps accounts for most of the variability in G1 and cell cycle time.
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PMID:Kinetic analysis of regulatory events in G1 leading to proliferation or quiescence of Swiss 3T3 cells. 386 Aug 68

We have previously shown that Swiss 3T3 cells located in the first part of G1 (post-mitotic G1 cells younger than 4.0 h or G1pm cells) were arrested after 9-10 h in the cell cycle by a short (1-8 h) exposure to serum-free medium or by a short (2-4 h) exposure to low doses of the protein synthesis inhibitor cycloheximide (CH). Kinetic data indicate that such G1pm cells rapidly return to G0 during this brief treatment and thereafter require a preparatory period of 8 h before continuing to G1. Cells older than 4 h, i.e. cells in mid or late G1 are already committed to DNA synthesis (presynthesis or G1ps cells). These cells as well as S and G2 cells were consequently unaffected by the brief serum starvation or the brief treatment with cycloheximide. In the present paper we show that the 10-h intermitotic delay that follows a 1-2 h exposure to serum-free medium can be completely counteracted by the presence of any one of the purified growth factors, epidermal growth factor (EGF), insulin or platelet-derived growth factor (PDGF). In contrast, the intermitotic delay following a longer exposure (8 h) to serum-free medium could no longer be counteracted by EGF or insulin. However, PDGF was still active in this respect. Most interestingly, the 12 h gross intermitotic delay induced by a 4h exposure to CH could be efficiently counteracted by EGF, PDGF or insulin. However, this effect on CH-treated cells could be counteracted by the growth factor only in the presence of 10% serum. This indicates the existence of a cooperative effect between PDGF, EGF or insulin and an unidentified serum factor. The effects on the cell cycle time of brief serum starvation and exposure to CH were compared with the effects on rate of protein synthesis and degradation. Although the effects of serum starvation on protein synthesis and degradation were found to be partially normalized by growth factors, we suggest that growth factors prevent cells from leaving the cell cycle by another mechanism and not merely by affecting the level of overall protein accumulation.
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PMID:Cell-cycle-specific induction of quiescence achieved by limited inhibition of protein synthesis: counteractive effect of addition of purified growth factors. 389 88

The effect of human platelet factors and purine derivatives on DNA synthesis has been investigated in mouse fibroblast-like L cells whose growth was arrested by serum starvation. When such cells were exposed to diluted platelet extract (e.g., 35 micrograms of protein per ml), a stimulatory effect on net DNA synthesis was observed. This effect was almost abolished by dialysis of the extract. The stimulation was, however, recovered by supplementing the diluted and dialyzed extract with hypoxanthine or adenosine. Similar phenomena were observed in pulse-labeling experiments performed with [3H]thymidine. In this case, however, there was a marginal stimulatory effect of adenosine or hypoxanthine alone. When the cells were treated with saturating concentrations of pure platelet-derived growth factor (PDGF), a stimulatory effect on pulse labeling was again obtained by the simultaneous presence of hypoxanthine or adenosine. In serum-starved cells of a mutant line of L cells deficient in hypoxanthine phosphoribosyltransferase, there was, however, no stimulatory effect on pulse labeling by hypoxanthine when it was added alone or together with either PDGF or diluted dialyzed platelet extract. It is suggested that the stimulation of DNA synthesis by the purine derivatives in the presence of a certain type of platelet proteins, probably involving PDGF, may be explained by their function as precursors for a purine ribonucleotide pool that is specifically related to DNA synthesis. Treatment of serum-starved L cells with high concentrations of dialyzed platelet extract (e.g., 240 micrograms of protein per ml) showed that platelets contain an additional type of factor that may substitute for the requirement of adenosine or hypoxanthine for DNA synthesis to take place. It is suggested that the effect of this type of factor may be to activate the catabolic activity of the purine salvage pathway.
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PMID:Both hypoxanthine and adenosine stimulate DNA synthesis independently in serum-starved L cells treated with platelet protein. 658 64

The state of induction of the platelet-derived growth factor (PDGF) A chain markedly differs among drugs and cells. The increase in A chain mRNA by serum was due to activation of transcription. Transcription was also activated by cycloheximide (CHX) even during serum starvation, indicating that the expression of the PDGF-A chain is inhibited by transcription suppressor factor with a short life during serum starvation. On the other hand, post-transcriptional regulation played a very important role in the increase in A chain mRNA by 12-O-tetradecanoylphorbol-13-acetate (TPA) and superinduction by TPA and CHX. We also analyzed the regions of PDGF-A chain gene that respond to serum and TPA by the chloramphenicol acetyltransferase (CAT) assay and the gel retardation assay. The region from TATA to -135 bp has the activity of the basal expression of PDGF-A chain gene and is considered to be involved in down regulation after the treatment with serum and TPA. Elements that respond to serum and increase the expression of PDGF-A chain gene are present in the region from -135 bp to -223 bp. Elements that inhibit the expression of PDGF-A chain gene during serum starvation are present in the region from -223 bp to -416 bp.
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PMID:Mechanism of regulation of PDGF-A chain gene expression by serum and TPA. 784 Nov 94

The role of Ca2+ and Zn2+ in the initiation of DNA synthesis in NIH 3T3 fibroblasts and c-Ha-ras(val-12) oncoprotein-expressing (NIH 3T3) cells has been studied. Entrapment of the Ca2+ chelator, BAPTA (30 microM), into the cells totally blocked a serum-induced rise in cytosolic free Ca2+ ([Ca2+]i) as determined with fura-2. Serum starvation for 24 h considerably reduced DNA synthesis in control NIH 3T3 fibroblasts. BAPTA treatment reduced serum-induced DNA synthesis and totally inhibited platelet-derived growth factor-induced DNA synthesis in these cells. DNA synthesis of the c-Ha-ras(val-12)-expressing fibroblasts was little affected by serum starvation and unaffected by entrapment of BAPTA into the cells. Intracellular Zn2+ was measured using the fluorescent probe TSQ in intact cells. As determined using image analysis the TSQ fluorescence was distributed throughout the cytoplasm and concentrated around the nucleus. The permeable Zn2+ chelator, TPEN, at a concentration of 10 microM, caused a maximal reduction in TSQ-available Zn2+. This concentration of TPEN totally blocked DNA synthesis both in control and c-Ha-ras(val-12)-expressing fibroblasts. Upon addition of 11 microM Zn2+ DNA synthesis was restored even after TPEN addition. [3H]Thymidine incorporation itself was also sensitive to TPEN treatment. The results suggest that c-Ha-ras(val-12)-induced proliferation is independent of changes in [Ca2+]i. A specific role of Zn2+ in c-Ha-ras-induced proliferation is unlikely since ras-expressing and control cells reacted similarly to Zn2+ deprivation. There seems to be a constant requirement for the presence of Zn2+ in cell proliferation.
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PMID:Ca2+ and Zn2+ dependence of DNA synthesis in untransformed and in Ha-ras(val-12)-expressing NIH 3T3 cells. 835 24

Using the Escherichia coli lacZ gene to identify chromosomal loci that are transcriptionally active during growth arrest of NIH 3T3 fibroblasts, we found that an mRNA expressed preferentially in serum-deprived cells specifies the previously characterized alpha-receptor (alphaR) for platelet-derived growth factor (PDGF), which mediates mitogenic responsiveness to all PDGF isoforms. Both PDGFalphaR mRNA, which was shown to include a 111-nt segment encoded by a DNA region thought to contain only intron sequences, and PDGFalphaR protein accumulated in serum-starved cells and decreased as cells resumed cycling. Elevated PDGFalphaR gene expression during serum starvation was not observed in cells that had been transformed with oncogenes erbB2, src, or raf, which prevent starvation-induced growth arrest. Our results support the view that products of certain genes expressed during growth arrest function to promote, rather than restrict, cell cycling. We suggest that accumulation of the PDGFalphaR gene product may facilitate the exiting of cells from growth arrest upon mitogenic stimulation by PDGF, leading to the state of "competence" required for cell cycling.
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PMID:The platelet-derived growth factor alpha-receptor is encoded by a growth-arrest-specific (gas) gene. 864 52

The intracellular effects of bradykinin are mediated through the recently cloned B2 kinin receptor which belongs to the superfamily of receptors with seven transmembrane domains. The molecular events which transduce the bradykinin signal on the post-receptor level are not understood in detail. We studied whether in human foreskin fibroblasts bradykinin treatment induces tyrosine phosphorylation of cellular proteins. Using phosphotyrosine antibodies we detected a bradykinin-dependent phosphorylation of a group of proteins of about 130 kDa and an additional signal around 70kDa after starvation of cells. The effect evoked by 10 nM bradykinin was rapid (2 min) and it was partially reduced by the B2-kinin-receptor antagonist Hoe 140 which was shown to be a weak inducer of tyrosine phosphorylation. The bradykinin-mediated tyrosine phosphorylation events were reproduced in human embryonal kidney 293 fibroblasts which were transiently transfected with the rat B2 kinin receptor, but they were not observed in untransfected 293 control cells. These data suggest that the B2 kinin-receptor subtype is involved. Upon fractionation of cells the 130kDa protein group was recovered both in the membrane and the cytosolic protein fraction. To assess the specificity of this bradykinin effect we stimulated human foreskin fibroblasts with epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-I) and insulin. While IGF-I, insulin and EGF were almost ineffective, PDGF stimulated the tyrosine phosphorylation of 130-kDa bands with a similar pattern to that produced by bradykinin. Immunoprecipitation experiments with specific antibodies against potential candidate proteins in the molecular-mass range around 130kDa revealed positive results for the focal adhesion kinase FAK and the p130 Src substrate while negative results were obtained for the GTPase-activating protein GAP, the phospholipase C-gamma1, the Janus kinase JAK-1 and vinculin. The data suggest that the tyrosine phosphorylation of FAK and the pl30 Src substrate might be involved in the B2-kinin-receptor signalling cascade.
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PMID:Bradykinin induces tyrosine phosphorylation in human foreskin fibroblasts and 293 cells transfected with rat B2 kinin receptor. 866 18


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