UMLS:C0038187 - FACTA Search

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

Continuous monitoring of fluorescence (CMF) has been used to examine doxorubicin efflux from intact human myeloma cells. The time resolution of these measurements has enabled detailed comparison of the initial rates of efflux for the drug-sensitive myeloma line RPMI 8226 and a series of sequentially derived multidrug-resistant (MDR) lines expressing different amounts of human MDR protein (P-glycoprotein). Cells that are 3-, 10-, 60-, or 120-fold resistant to doxorubicin export approximately 10, 20, 30, or 33% more doxorubicin than the parental sensitive cells, respectively, when all are preloaded to the same level of total intracellular drug. Remarkably, however, when cells are loaded to the same level of exchangeable drug the initial rates of efflux are found to be virtually identical. This agreement between rates is apparently not dependent on the drug concentration. Approximately 50% of the increase in the steady-state level of doxorubicin efflux for the resistant cells is abolished upon glucose starvation. However, surprisingly, the apparent initial rates of efflux from the treated and untreated cells are found to be virtually the same. Pretreatment of the resistant cells with verapamil reduces the steady-state level of efflux but increases the apparent initial rate at some concentrations. Conversely, vincristine does not alter steady state but slows the initial rate of efflux from both sensitive and resistant cells by approximately the same extent. Finally, quite interestingly, a nearly linear relationship between pHi and relative steady state of efflux is found for the series of cell lines. These data are interpreted in terms of existing models for MDR.
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PMID:Analysis of the steady-state and initial rate of doxorubicin efflux from a series of multidrug-resistant cells expressing different levels of P-glycoprotein. 136 58

Terminal deoxynucleotidyl transferase (TdT) is a template-independent DNA polymerase that is transiently expressed during the normal development of T and B lymphocytes. Phorbol 12-myristate 13-acetate (PMA) has been reported to induce maturation-like changes, including the loss of TdT, in many leukemic cell lines. We investigated the mechanism of TdT repression by PMA in an early thymocyte-like cell line, RPMI 8402. At a concentration of 8 nM, PMA caused both repression of TdT synthesis and arrest of proliferation. At greater concentrations of PMA, these same changes initially occurred, but then cell proliferation resumed, and TdT was reexpressed. At both 8 and 160 nM PMA, TdT biosynthesis and TdT mRNA became undetectable within 8 hours, while cell proliferation and DNA synthesis were not significantly reduced until 16 hours. Growth arrest induced by serum starvation did not result in a similar reduction of TdT RNA even after 48 hours. With 160 nM PMA, TdT mRNA could be detected again by 24 hours, and proliferation resumed. Transcription run-off assays indicated that TdT RNA synthesis ceased within 1 hour after exposure to both 8 and 160 nM PMA. T cell receptor alpha (TcR alpha) RNA was induced when TdT RNA was repressed. TcR beta RNA levels were unchanged, and TcR gamma RNA was up-regulated. TdT gene repression and modulation of cell proliferation as well as induction of TcR gene expression are normal events during intrathymic T cell maturation. This cell model provides a system for analyzing the molecular regulation of these significant developmental events.
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PMID:Phorbol ester regulation of terminal deoxynucleotidyl transferase, proliferation, and TcR alpha in a pre-T cell line. 213 60

We have studied the transcription of the argininosuccinate synthetase gene in cultured RPMI 2650 cells under conditions where the enzyme is subject to metabolite regulation and in canavanine-resistant variants (Canr1 cells) which overproduce the enzyme greater than 200-fold. When grown continuously in medium with citrulline substituted for arginine, the argininosuccinate synthetase activity of RPMI 2650 cells increases 5- to 10-fold. In these cells, expression of a transfected minigene containing the 5'-flanking region of the argininosuccinate synthetase gene was increased 20-fold by short term starvation for arginine and 10-fold by short term starvation for leucine. Levels of nuclear RNA from the first intron of the gene correlated with enzyme activity; i.e. RPMI 2650 cells cultured in arginine medium less than RPMI 2650 cells cultured in citrulline medium less than Canr1 cells. Run-off transcription experiments showed that the transcription of argininosuccinate synthetase increased in RPMI 2650 cells starved for either arginine or leucine. While expression of the minigene and the transcription rate for argininosuccinate synthetase were increased during 48 to 72 h of starvation, the endogenous enzyme activity did not increase in RPMI 2650 cells. Amino acid starvation did not affect the rate of transcription of argininosuccinate synthetase in Canr1 cells. The results indicate that the steady state levels of argininosuccinate synthetase expression in Canr1 cells and in citrulline-adapted RPMI 2650 cells are largely determined by the rate of transcription. The failure of increased transcription rate to correlate with increased enzyme activity during acute starvation for arginine or leucine may suggest the involvement of post-transcriptional regulatory mechanisms for argininosuccinate synthetase or may merely be due to amino acid deprivation. The finding that leucine starvation has effects similar to arginine starvation raises the question of whether mammalian cells have general control mechanisms which are similar to the general control of amino acid biosynthesis in Saccharomyces cerevisiae.
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PMID:Metabolite regulation of argininosuccinate synthetase in cultured human cells. 318 97

Regulation of argininosuccinate synthetase (AS) was studied by using minigenes containing 3 kilobases of DNA upstream from the TATAA box and 9 kilobases downstream (including the first four exons of the AS gene) ligated to either the cDNA for AS or to the chloramphenicol acetyltransferase (CAT) gene. Unlike the endogenous AS gene, expression of the CAT minigene was not elevated in Canr1 cells, which overproduce AS compared with parental RPMI-2650 cells. Expression of the CAT minigene in both stable and transient analyses was four- to five-fold higher in RPMI-2650 cells grown in citrulline medium than in cells grown in arginine medium. Although endogenous AS activity is not subject to metabolite regulation in Canr1 cells and expression of the CAT minigene in Canr1 cells was not increased when cells were grown in citrulline medium, expression of the CAT minigene was 10- to 22-fold greater when intracellular arginine pools were depleted by transient starvation for arginine and citrulline.
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PMID:Arginine-mediated regulation of an argininosuccinate synthetase minigene in normal and canavanine-resistant human cells. 378 95

Fas belongs to the family of type-1 membrane proteins that transduce apoptotic signals. In the present studies, we characterized signaling during Fas-induced apoptosis in RPMI-8226 and IM-9 multiple myeloma (MM) derived cell lines as well as patient plasma cell leukemia cells. Treatment with anti-Fas (7C11) monoclonal antibody (MoAb) induced apoptosis, evidenced by internucleosomal DNA fragmentation and propidium iodide staining, and was associated with increased expression of c-jun early response gene. We also show that anti-Fas MoAb treatment is associated with activation of stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (MAPK); however, no detectable increase in extracellular signal-regulated kinases (ERK1 and ERK2) activity was observed. Because interleukin-6 (IL-6) is a growth factor for MM cells and inhibits apoptosis induced by dexamethasone and serum starvation, we examined whether IL-6 affects anti-Fas MoAb-induced apoptosis and activation of SAPK or p38 MAPK in MM cells. Culture of MM cells with IL-6 before treatment with anti-Fas MoAb significantly reduced both DNA fragmentation and activation of SAPK, without altering induction of p38 MAPK activity. These results therefore suggest that anti-Fas MoAb-induced apoptosis in MM cells is associated with activation of SAPK, and that IL-6 may both inhibit apoptosis and modulate SAPK activity.
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PMID:Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. 897 96

Depressed cell-mediated immunity and decreased insulin-like growth factor I (IGF-I) are observed in malnourished humans. To study the interaction among nutrition, IGF-I, and cytokines, healthy volunteers (six men and four women, aged 21-38 yr, weighing 93-124% of ideal body weight) were subjected to a 7-day fast (mineral water only). Fasting steadily decreased serum IGF-I from 247 +/- 29 (prefast) to 87 +/- 10 ng/mL (postfast; P < 0.0001), total T cells (CD3+) from 1499 +/- 68 to 1308 +/- 70 x 10(9) (P < 0.0001), and T helper cells (CD4+) from 997 +/- 62 to 856 +/- 55 x 10(9) (P < 0.001). Peripheral blood mononuclear cells were isolated and cultured in serum-free RPMI 1640 for 24 h. Fasting attenuated peripheral blood mononuclear cell production of interleukin-2 in response to various concentrations of phytohemagglutinin P [PHA-P; 347 +/- 48 (prefast) vs. 135 +/- 52 pg/mL (postfast) when challenged with 3 micrograms/mL PHA-P; P < 0.005 when comparing dose-response curves (1-100 micrograms/mL PHA-P)]. Although the approximately 3-fold suppression of interleukin-2 and IGF-I in subjects fasted for 1 week is not likely to affect immune function significantly, our results with this short term model of nutrient restriction provide insight into possible mechanisms for immune suppression in chronic starvation.
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PMID:Decreased interleukin-2 production from cultured peripheral blood mononuclear cells in human acute starvation. 910 May 92

It has been demonstrated previously that motile Borrelia burgdorferi cells transform into non-motile cyst-forms when incubated for several weeks in BSKII (a complex medium) lacking rabbit serum. B. burgdorferi cells cannot synthesize fatty acids de novo and serum is thought to provide a source of fatty acids and lipids. When B. burgdorferi cells were serum-starved in defined RPMI medium, -90% of the cells formed spherical cysts within 48 h. Cyst formation was inhibited by tetracycline. Cyst opening and recovery of vegetative cells was rapidly induced by the addition of either BSKII or rabbit serum. The percentage of viable cells recovered from cysts ranged from 2.9% to 52-5%. Viability was inversely proportional to cyst age. Protein synthesis by B. burgdorferi during serum starvation was examined by labelling cells with Tran35S-Label and analysing the labelled proteins by two-dimensional gel electrophoresis and fluorography. The synthesis of over 20 proteins was induced during serum starvation. Western blots of proteins from vegetative cells and cysts probed with sera from either B. burgdorferi-infected humans or monkeys revealed that several cyst proteins were antigenic. These data suggest that cells of B. burgdorferi, although possessing a small genome and extremely limited biosynthetic capabilities, rapidly respond to conditions of serum starvation by inducing changes in protein synthesis and cell morphology. This study may help explain how cells of B. burgdorferi can survive periods of nutrient deprivation in different hosts and host tissues.
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PMID:Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi. 1065 58

AIM:To determine the relationship between serum deprivation or serum levels and cell proliferation of human hepatoma SMMC-7721 cells.METHODS:Human hepatoma SMMC-7721 cells were grown in RPMI 1640 supplemented with 10% fetal calf serum (FCS)in 5% CO(2) incubator at 37&mgr; for 24h, and culture media were replaced to serum-free or different serum FCS levels (2.5%, 5%, 10%, 20% and 25%). Six h,12h,18h and 24h after the culture,the cells were incorporated &mgr;(3)H&mgr;-TdR for 4h. At last &mgr;(3)H&mgr;-TdR incorpor-ation was detected with liquid scintillation counting.RESULTS:DNA synthesis of SMMC-7721 cells could be sharply stimulated by short-time (6h) serum deprivation (the cpm value of (3)H-TdR incorporation of cells in serum-free was 39.32-fold higher than cells in 25% serum),and the incorporation of (3)H-TdR was negatively related to the serum levels.Longer-time serum starvation (12h, 18h and 24h) also greatly stimulated DNA synthesis, although the cpm value of (3)H-TdR incroporation was less than that in 6h serum deprivation. Morphology of cells cultured in different serum levels also showed significant difference.CONCLUSION:Compared with other cell lines such as BEL7404 and Swiss 3T3,human hepatoma SMMC-7721 cells had different response to the serum deprivation.Short-time serum deprivation could greatly stimulate DNA synthesis of human hepatoma SMMC-7721 cells.Precautions must be given to the changes of serum levels for the detection of growth factors and drugs using SMMC-7721 cells as a model.
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PMID:Serum deprivation enhances DNA synthesis of human hepatoma SMMC7721 cells. 1181 53

Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted by the tick Ixodes scapularis. A 2.9-kb fragment containing a putative spoT gene was isolated from B. burgdorferi genomic DNA by PCR amplification and cloned into a pBAD24 vector. The cloned gene complemented Escherichia coli mutant strain CF1693, which contains deletions of both the relA and spoT genes. The spoT gene in E. coli encodes a bifunctional enzyme capable of synthesizing and degrading (p)ppGpp, which mediates the stringent response during carbon source starvation. B. burgdorferi has been reported to have a stress response to serum starvation. Thin-layer chromatography was used to detect (p)ppGpp extracted from H(3)(32)PO(4)-labeled B. burgdorferi cells starved for serum in RPMI. B. burgdorferi spoT gene expression was characterized during fatty acid starvation. Northern analysis of spoT revealed detectable message at 2.5 min of starvation in RPMI. Expression of spoT during serum starvation increased approximately 6-fold during the 30 min that starvation conditions were maintained. Further, expression of spoT decreased when serum was added to serum-starved cells. Reverse transcriptase PCR (RT-PCR) was used to detect spoT mRNA from approximately 10(6) cells starved for serum in RPMI for 2.5 to 30 min or incubated in tick saliva for 15 min. Northern blot analysis suggests that spoT transcript was approximately 900 nucleotides in length. RT-PCR amplification of the transcript using several sets of primers confirmed this finding. Additionally, a truncated clone containing only the first 950 bp of the 2,001-bp spoT open reading frame was able to complement E. coli CF1693. The data suggest that B. burgdorferi exhibits a stringent response to serum starvation and during incubation in tick saliva.
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PMID:Expression of spoT in Borrelia burgdorferi during serum starvation. 1251 89

The cell growth is controlled by the interaction of survival and cell growth arrest pathways as well as apoptosis mechanisms which determine the outcome of cell faith as proliferation or apoptosis. In this study, we have studied the activity of survival pathways, i.e., Akt and ERK1/2 with regard to XIAP (inhibitor of apoptosis) in serum starved and stimulated conditions. The HEK-293 cells were cultured in RPMI + 10% FBS. The cells were serum starved by switching to medium with 1% FBS for 24 h and serum stimulated by changing the medium to 10% FBS following serum starvation. The expression of p-Akt, p-ERK, Akt, ERK and XIAP was studied in various time points using western blot. The apoptosis was evaluated by DNA condensation using Hoechst 33258 and Caspase-3 assay. In serum starved condition expression of p-Akt and XIAP is very low. Serum stimulation increases p-Akt and p-ERK within 5 min and sustains a high level for 30 min. The expression of total Akt and ERK1/2 has not changed significantly for 24 h. XIAP expression starts at 6 h after serum stimulation, reaches to maximum level at 12 h and decreases to baseline within 24 h. Furthermore, serum starvation for 24 h does not induced apoptosis and DNA condensation. Taken together, the results indicate that serum activates Akt and ERK pathways earlier than XIAP expression. Furthermore, XIAP expression is low in serum starvation unlike p-ERK which suggests a survival role for ERK in serums starvation. The expression pattern of XIAP indicates induction by Akt and/or ERK activation which requires further studies.
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PMID:The time course of Akt and ERK activation on XIAP expression in HEK 293 cell line. 1964 22

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