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

In eukaryotic cells, nucleus-cytoplasm exchanges play an important role in genomic regulation. We have analyzed the localization of four nuclear antigens in different growth conditions: two replicative proteins, DNA polymerase alpha and proliferating cell nuclear antigen (PCNA), and two oncogenic regulatory proteins, c-Myc and c-Fos. A kinetic study of subcellular localization of these proteins has been done. In cultures in which cells were sparse, these proteins were detected in the nucleus. When proliferation was stopped by the high density of culture cells or by serum starvation, these proteins left the nucleus for the cytoplasm with different kinetics. DNA polymerase alpha is the first protein to leave the nucleus, with the PCNA protein, c-Fos, and c-Myc leaving the nucleus later. In contrast, during serum stimulation c-Fos and c-Myc relocalize into the nucleus before the replicative proteins. We also noticed that in sparse cell cultures, 10% of the cells exhibit a perinuclear staining for the DNA polymerase alpha, PCNA, and c-Myc proteins but not for c-Fos. This peculiar staining was also observed as an initial step to nuclear localization after serum stimulation and in vivo in Xenopus embryos when the G1 phase is reintroduced in the embryonic cell cycle at the mid-blastula stage. We suggest that such staining could reflect specific structures involved in the initiation of the S phase.
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PMID:Comparative analysis of the intracellular localization of c-Myc, c-Fos, and replicative proteins during cell cycle progression. 135 52

Human autoimmune sera specific for proliferating cell nuclear antigen (PCNA)/cyclin (auxiliary protein for DNA polymerase delta) demonstrated the presence of epitopes within the macro- and micronuclei of the hypotrichous ciliated protozoa Euplotes eurystomus. Tightly bound PCNA/cyclin was localized at the site of DNA synthesis in macronuclei, the rear zone of the replication band. Starvation or heat shock, conditions that reduce macronuclear replication, resulted in a decrease of PCNA/cyclin in replication bands. Micronuclei also exhibited PCNA/cyclin localization which persisted for a large proportion of the vegetative cell cycle and exhibited significant resistance to adverse culture conditions. Immunoprecipitation of 35S-labeled soluble Euplotes proteins with PCNA/cyclin autoimmune sera revealed a spectrum of low molecular mass proteins. PCNA/cyclin-like proteins have now been observed in the widely divergent species: human, rat, amphibian, yeast, and ciliated protozoa.
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PMID:Proliferating cell nuclear antigen/cyclin in the ciliate Euplotes eurystomus: localization in the replication band and in micronuclei. 247 76

PC10 is a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The staining pattern in immunochemistry depends on fixation and detergent extraction treatment. The aim of this study was to validate the flow cytometric PCNA assay against Bromodeoxyuridine-labelling index (BrdUrd-LI) under different proliferative conditions in vitro. Expression of PCNA in methanol fixed cells with, and without, prior detergent extraction with EDTA/Triton was compared to BrdUrd-labelling index in NIH-3T3 fibroblasts and human Caski tumour cells in exponential phase and under confluent conditions. Serum stimulation and serum starvation conditions were studied. The results for BrdUrd-LI and PCNA-index after extraction showed good correlation for 3T3 fibroblasts and for Caski cells, with some differences for serum withdrawn Caski cells. There was no correlation between the number of cells that were positive for PCNA without extraction and BrdUrd-LI. Spheroid cells with G1-DNA-content showed an almost synchronous recruitment and progression through the cell cycle after trypsination and replating. Tightly bound PCNA paralleled this synchronicity whereas total PCNA did not change significantly. The results demonstrate that immunochemical detection of non-extractable PCNA-index gives similar results as compared with BrdUrd-labelling index under different proliferative conditions in vitro for different monolayer cell lines, whereas without extraction PCNA does not correlate with BrdUrd-LI in these fast growing cell lines due to its long half-life. PCNA expression parallels the progression through the cell cycle in V79 spheroids, a primitive model of tumour growth.
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PMID:Comparison of proliferating cell nuclear antigen (PCNA) staining and BrdUrd-labelling index under different proliferative conditions in vitro by flow cytometry. 789 42

Spontaneous amplification of bovine papillomavirus type 1 DNA occurs following a prolonged period of serum starvation of wild-type virus-transformed C127 cell lines and is associated with abundant viral E2 protein synthesis and a concomitant induction of viral oncogene (E5 and E6) expression. We show here that a subpopulation of the permissive cells incorporate bromo-deoxyuridine under conditions of cell growth arrest (serum starvation), whereas DNA synthesis is suppressed in the resting population of nonpermissive cells. Flow cytometric measurements of the cellular DNA content of the permissive cell population indicated that it contained predominantly a 4n DNA content, suggesting that these cells were blocked in the G2 phase of the cell cycle. In keeping with the hypothesis that viral DNA amplification is associated with the induction of a cellular S phase, we observed a specific induction of expression of two cell proliferation-related cellular antigens (PCNA and Ki67) in a subpopulation of permissive cells. C127 cell lines transformed by an E5-minus bovine papillomavirus type 1 mutant, which was competent for autonomous plasmid replication in mitotic cells, were completely defective for the induction of DNA synthesis and mutant viral DNA amplification under conditions of serum starvation. Moreover, the E5 protein is shown by immunofluorescence analysis to be expressed at a high level specifically in the permissive cell population. These results imply a dual role for the viral E5 protein in the C127 model system, both as a transforming protein and as a factor required for the induction of viral DNA amplification in postmitotic cells. We suggest that E5 acts at an early step in the induction of this process in C127 cells and may be required to turn on host cell DNA synthesis as a prerequisite for viral DNA amplification.
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PMID:Regulation of DNA synthesis in division-arrested mouse C127 cells permissive for bovine papillomavirus DNA amplification. 791 33

In normal human fibroblast cells, the primary cell cycle regulators, the cyclin-dependent kinases (CDKs), exist predominantly in multiple quaternary complexes, each consisting of a CDK, a cyclin, proliferating cell nuclear antigen (PCNA) and p21. p21 encodes a universal inhibitor of cyclin-dependent kinases. Here we show that the level of p21 mRNA and the interaction of p21 protein with cyclin-CDK enzymes are regulated during the cell cycle. When normal human fibroblast IMR90 cells were released from serum starvation, p21 mRNA reached its highest level immediately following serum stimulation, began to decrease at the G1/S boundary, fell to its lowest level during S phase, and accumulated again as cells exited from S phase. p21 protein associates with each cyclin-CDK complex in a cell cycle dependent manner. Cyclin A-CDK2-p21-PCNA and Cyclin B1-CDC2-p21-PCNA complexes are assembled in early S and G2 phase, respectively, indicating that p21 and/or PCNA regulates the enzymatic activity of each kinase at the time of their functioning. Cyclin D1-CDK4-p21-PCNA complexes, on the other hand, persist throughout the cell cycle, suggesting that cyclin D1-CDK4 quaternary complexes may play a role in monitoring an event(s) that may occur at any time, rather than at a specific stage of the cell cycle. The level of p21 mRNA in early passage Li-Fraumeni cells that are heterozygous for p53 mutation remained similar to that in normal fibroblasts, but was undetectable in immortalized Li-Fraumeni cells homozygous for mutant p53. This finding provides a plausible molecular explanation for the loss of genetic stability associated with cells homozygous, but not heterozygous, for p53 mutation.
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PMID:Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. 791 44

Differentially regulated expression of activators and inhibitors of cyclin-dependent kinases (cdks) modulate cell cycle progression. In normal fibroblasts, these complexes consist of the cdk inhibitor p21WAF1/PCNA/G1 cyclin/cdk. We now show that bromodeoxyuridine (BrdUrd), a thymidine analogue and radiation sensitizer, inhibits growth and activity of cyclin A-cdk2 kinase in metastatic C8161 and nonmetastatic neo 6.3/C8161 human melanoma cells. Inhibition is not due to altered levels of cyclin D or catalytic cdk2 but involves a decrease in cyclin A and proliferating cell nuclear antigen, paralleled by higher levels of p21WAF1 without increases in p53. In contrast to serum starvation, which prevents accumulation of cyclins A and D in normal fibroblasts, such treatment did not down-regulate either cyclin in these melanoma cells, implying an aberrant control for G1 cyclins in these tumor cells. However, cyclin A was decreased by BrdUrd, suggesting that this pyrimidine analogue arrests melanoma cells at a G1 transition point, unlike that of serum starvation. This is the first report indicating that the antitumor therapeutic action of BrdUrd may be mediated by a p53-independent reciprocal effect on activators and inhibitors of cdk kinases.
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PMID:p53-independent increase in p21WAF1 and reciprocal down-regulation of cyclin A and proliferating cell nuclear antigen in bromodeoxyuridine-mediated growth arrest of human melanoma cells. 882 3

Cell proliferation and differentiation are influenced by environmental factors, including the extracellular pH. We recently showed, using an ex vivo organ culture system of human mucosal Barrett's esophageal biopsies, that acid has a highly variable effect on cell proliferation and differentiation depending on the pattern of acid exposure. Study of the mechanisms underlying these dynamic effects of acid on this premalignant intestinal-like epithelium is hampered by lack of an immortalized cell line. We therefore investigated the effect of acid exposure on the human colonic carcinoma cell line HT29, chosen because of its intestinal cell derivation and its ability to differentiate in vitro. HT29 cells exposed to pH 5 medium either continuously (up to 3 weeks), or as a short (1 hour) pulse, were compared with cells cultured at pH 7.4. Villin expression was induced only by long term acid exposure, and correlated with the development of differentiated polarized cells that contain a brush border and microvillus inclusions. Chronic acid exposure arrested cell proliferation, whereas a 1 hour acid-pulse enhanced cell proliferation, as determined by [3H]thymidine incorporation assays and proliferating cell nuclear antigen expression. Serum starvation attenuated the hyperproliferative effect of an acid-pulse. In addition, the doubling time of at least the first cell cycle after an acid-pulse was shortened. The Na/H exchanger is likely to play a role since the hyperproliferative acid-induced response was blocked by amiloride; and the activity of the exchanger was increased at acidic pH as determined by 22Na uptake. These results support a role for extracellular pH on cell proliferation and differentiation of HT29 cells. Furthermore, these findings parallel the dynamic effects of acid on Barrett's esophagus, and suggest that HT29 cells could serve as an in vitro model for studying the mechanism of acid modulation in Barrett's esophagus.
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PMID:Acid modulation of HT29 cell growth and differentiation. An in vitro model for Barrett's esophagus. 909 48

The effect of posthatch starvation on skeletal muscle growth and satellite cell proliferation was examined in chicks. Chicks were either fed or starved for 48 h posthatch (d 0-d 2, d 2-d 4 or d 4-d 6) and then refed for 41 d. Body and breast muscle weights were significantly lower in starved chicks than in fed controls throughout the experiment. Histochemical staining revealed that skeletal muscle fiber development in the starved group lagged behind that of the fed group. Starvation from d 2 to 4 and d 4 to 6 posthatch had a progressively lesser effect than did immediate posthatch starvation (P < 0.05). In vitro culturing of breast muscle satellite cells revealed that DNA synthesis and number of cells per gram of muscle in the fed chicks peaked on d 2 and d 3, and then declined. In contrast, DNA synthesis in the cells of starved chicks declined on d 2 and increased on d 3 when chicks were refed. A similar pattern was seen for the number of cells per gram muscle; however, in general cell numbers tended to be higher in the starved group than in controls (P < 0.1). The results obtained with cultured cells were parallel with in situ immunostaining with 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen in breast muscle from experimental chicks, and with growth hormone receptor expression. These results suggest that satellite cell cultures are a reliable tool for evaluating muscle growth in postnatal chickens. We conclude that sufficient feed in the immediate postnatal period is critical for satellite cell proliferation and skeletal muscle development and is thus important for optimal muscle growth.
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PMID:Early posthatch starvation decreases satellite cell proliferation and skeletal muscle growth in chicks. 1073 42

To determine the crucial abnormality in the cell cycle regulatory proteins in human squamous cell carcinoma of the esophagus, we examined the cell growth ratio (CGR) and basal expression levels of G1 cyclins (cyclin D1, cyclin E), cyclin-dependent kinase (cdk) 2, cdk4, proliferating cell nuclear antigen (PCNA), and p21Waf-1 using 9 cell lines (KE3, KE4, TE8, TE9, TE10, TE11, YES1, YES2, and YES6). Western blotting revealed an inverse linear correlation between the basal levels of p21Waf-1 expression and CGR. The protein levels of G1 cyclins, cdks, and PCNA did not coordinately reflect the CGR. There was no relationship between p21Waf-1 expression levels and mutation of the p53 gene. Next, when the cells were stimulated with serum 48 h after the starvation, stimulated levels of the above G1 cell cycle markers were variously observed among cell lines irrespective of CGR. Serum stimulation markedly induced phosphorylated Rb in TE9 (a high CGR cell line, CGR>2.0), but not in KE4 (a low CGR cell line, CGR<1.5). Furthermore, adenovirus-mediated expression of exogenous p21Waf-1 effectively reduced cell growth in KE3 and TE9 (high CGR cell lines), but not in KE4 and TE11 (low CGR cell lines). p21Waf-1-mediated growth suppression was associated with the induction of involucrin, a marker of squamous cell differentiation. Our data suggested that the basal level, but not the stimulated level, of p21Waf-1 expression play a pivotal role in abnormal growth in human squamous cell carcinoma of the esophagus.
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PMID:Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus. 1111 54

It was shown previously [Riedinger, H. J., van Betteraey-Nikoleit, M & Probst, H. (2002) Eur. J. Biochem.269, 2383-2393] that initiation of in vivo SV40 DNA replication is reversibly suppressed by hypoxia in a state where viral minichromosomes exhibit a nearly complete set of replication proteins. Reoxygenation triggers fast completion and post-translational modifications. Trying to reveal such fast changes of chromatin-bound replication proteins in the much more complex replication of the cellular genome itself, we developed a protocol to extend these studies using the human bladder carcinoma cell line T24, which was presynchronized in G1 by starvation. Concomitantly with stimulation of the cells by medium renewal, hypoxia was established. This treatment induced T24 cells to contain a large amount of replicons arrested in the 'hypoxic preinitiation state', ready to initiate replication as soon as normal pO2 was restored. Replicons in other stages of replicative activity were not detectable. Consequently the arrested replicons were rapidly released into synchronous initiation and succeeding elongation. Extraction of T24 nuclei with a Triton X-100 buffer yielded a fraction containing the cellular chromatin, including DNA-bound replication proteins, while unbound proteins were removed. The usefulness of this protocol was tested by the proliferation marker PCNA. We demonstrate here that this protein switches from the remainder cellular protein pool into the Triton-extracted nuclear fraction upon reoxygenation. Employing this protocol, analyses of chromatin-bound MCM2, MCM3, Cdc6 and cdk2 suggests that the 'classical' prereplication complex is already formed during hypoxia.
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PMID:Analyzing changes of chromatin-bound replication proteins occurring in response to and after release from a hypoxic block of replicon initiation in T24 cells. 1451 70


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