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)

We have previously demonstrated in transient expression assay systems that a human multidrug resistance 1 (MDR1) promoter can be directly activated by cytotoxic anticancer agents. In this study, we examined whether the MDR1 promoter could be regulated in response to growth arrest induced by serum starvation. We have established human and rodent cell lines which stably expressed the chloramphenicol acetyltransferase (CAT) gene driven by various lengths of the MDR1, the viral thymidine kinase (TK) and the simian virus 40 (SV40) promoters. Serum starvation caused enhanced expression of CAT gene with MDR1 promoter, but not with two viral gene promoters in human cancer KB cells. Hydroxyurea activated the MDR1 promoter, but not TK and SV40 promoters. By contrast, the DNA topoisomerase II inhibitor, etoposide, equally activated the MDR1, TK and SV 40 promoters. Increased CAT gene expression by serum starvation was also specifically observed in stable transfectants of human adrenal SW-13 cell lines, but not in stable transfectants of mouse fibroblast NIH3T3 and adrenal Y-1 cell lines when the human MDR1 promoter-CAT was introduced. Etoposide, however, effectively induced CAT activity in both human and rodent cells. Assays with deletion constructs of the MDR1 promoter showed that serum starvation activated the MDR1 promoter carrying -258 approximately +121 base sequence of the promoter, but not -198 approximately +121 of the promoter. These results suggest that the expression of the MDR1 gene induced by serum starvation is regulated at the transcriptional level in a promoter sequence-specific manner in human cells.
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PMID:The human multidrug resistance 1 promoter has an element that responds to serum starvation. 155 May 97

The positioning of replicated chromosomes at one-fourth and three-fourths of the cell length was inhibited when protein synthesis was inhibited by chloramphenicol or rifampin or by starvation for amino acids. Under these conditions, the progress of chromosome replication continued and replicated chromosomes were located close to each other as one nucleoid mass at midcell. Cells which already had two separate daughter chromosomes located at the cell quarters divided into two daughter cells under these conditions. When protein synthesis resumed, daughter chromosomes moved from midcell to the cell quarters, respectively, before any detectable increase in cell length was observed. The chromosome positioning occurred even under inhibition of the initiation of chromosome replication and under inactivation of DNA gyrase. The chromosome positioning presumably requires new synthesis of a particular protein(s) or translation itself.
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PMID:Positioning of replicated chromosomes in Escherichia coli. 215 7

We have examined the roles of eukaryotic DNA topoisomerases I and II in DNA replication by the use of a set of four isogenic strains of Saccharomyces cerevisiae that are TOP1+ TOP2+, TOP1+ top2 ts, delta top1 TOP2+, and delta top1 top2 ts. Cells synchronized by treatment with the alpha-mating factor, or by cycles of feeding and starvation, were released from cell-cycle arrest, and the size distribution of DNA chains that were synthesized after the cells reentered the S-phase was determined as a function of time. The results indicate that synthesis of short DNA chains several thousand nucleotides in length can initiate in the absence of both topoisomerases, but their further elongation requires at least one of the two topoisomerases. Inactivation of DNA topoisomerase II does not alter significantly the time dependence of the patterns of nascent DNA chain synthesis, which is consistent with the notion that the requirement of this enzyme for viability is due to its essential role during mitosis, when pairs of intertwined newly replicated chromosomes are being segregated. The absence of DNA topoisomerase I leads to a temporary delay in the extension of the short DNA chains; this delay in chain elongation is also reflected in the rate of total DNA synthesis in the delta top1 mutant during the early S-phase. Thus, in wild-type cells, DNA topoisomerase I is probably the major replication swivel. The patterns of DNA synthesis in asynchronously grown delta top1 top2 ts cells at permissive and non-permissive temperatures are also consistent with the above conclusions.
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PMID:Function of DNA topoisomerases as replication swivels in Saccharomyces cerevisiae. 254 54

The intracellular level of DNA topoisomerase II appears to be reversibly regulated by serum concentration in cultured primary human skin fibroblasts (HSF). Upon serum starvation, the intracellular level of topoisomerase II in HSF, as monitored by immunoblotting with antitopoisomerase II antibodies, gradually decreased to a nondetectable level (less than 10(4) copies/cell) over a period of 72 h. Addition of 10% serum to the starved cells led to a gradual increase of the intracellular topoisomerase II to the original level (approximately 10(6) copies/cell) over a period of 24 h. The intracellular DNA topoisomerase II level in HSF is also sensitive to cell density; minimally a 7-fold decrease was observed when HSF were grown to saturation density in a constant serum concentration. Similarly, the intracellular levels of DNA topoisomerase II in other "nontransformed" cells such as mouse NIH 3T3 and 3T6 cells are also sensitive to both the serum concentration and the cell density. In contrast, topoisomerase II levels in transformed cells such as HeLa cells, L1210 cells, and SV40 T-antigen-transformed COS-1 cells are maintained at high levels (approximately 10(6) copies/cell) and are much less sensitive to growth conditions. The topoisomerase II level in HeLa cells synchronized by a double thymidine block remained relatively constant (less than 2-fold difference) throughout the late G1, S, G2, and M phases of the cell cycle. Our results suggest that the level of DNA topoisomerase II is primarily regulated in the G0-G1 phase of the cell cycle and is elevated to a high level (approximately 10(6) copies/cell) in proliferating cells. In contrast, the intracellular levels of DNA topoisomerase I in these cells were largely unaffected by these growth conditions either in HSF or in HeLa cells.
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PMID:Proliferation-dependent regulation of DNA topoisomerase II in cultured human cells. 283 57

Ciprofloxacin and other newer quinolone antimicrobial agents exhibit increased potency and decreased frequency of spontaneous bacterial resistance in comparison with older analogues such as nalidixic acid. New and published observations on the mechanisms of action of and resistance to ciprofloxacin in Escherichia coli are presented and discussed. Genetic and biochemical studies have identified the A subunit of the essential bacterial enzyme DNA gyrase as a target of ciprofloxacin and other quinolones. For a series of quinolones, inhibition of purified DNA gyrase correlated with antibacterial activity. The bactericidal activity of ciprofloxacin and ofloxacin is, in contrast to that of certain other quinolones, somewhat less affected by rifampin and cell starvation, suggesting the existence of a site of drug action in addition to DNA gyrase. The frequency of selection of spontaneous single-step resistance mutants of E. coli was more than 100-fold lower with ciprofloxacin than with nalidixic acid. Strains highly resistant to ciprofloxacin could, nevertheless, be selected by serial passage on drug-containing agar. Two mutations contributing to this high level of resistance were analyzed. One, designated cfxA, conferred a 16-fold increase in drug resistance and mapped in a location consistent with a gyrA mutation; similar increases in resistance to ciprofloxacin were seen with gyrA mutations selected for resistance to other quinolones. The other mutation, cfxB, conferred pleiotropic resistance to ciprofloxacin, tetracycline, and chloramphenicol and appeared to be an allele of the multiple antibiotic resistance gene marA. The mutation cfxB was associated with a decreased amount of porin outer membrane protein OmpF, suggesting that drug permeation may occur in part through this channel. In summary, the A subunit of DNA gyrase is a target of ciprofloxacin and other quinolones. Ciprofloxacin resistance appears to occur both by mutation in this target and by alteration of drug permeation through the outer membrane of the cell.
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PMID:Mechanisms of action of and resistance to ciprofloxacin. 303 57

When the dnaB37 initiation mutant of Bacillus subtilis is returned to a permissive temperature following a period at 45 degrees C, a synchronous round of DNA replication immediately ensues. Using this system we have been able to analyse the first fragments to be replicated while avoiding the use of thymine starvation or inhibitors of DNA replication. Such treatments are necessary to achieve even modest synchrony in germinating spores. Our results showed that the first fragment to be replicated was a 4 kb BamHI-SalI restriction fragment, BS6. In contrast, when the analysis was performed out in the presence of novobiocin, an inhibitor of DNA gyrase, replication from BS6 was inhibited and the first fragment to be replicated was BS5, a 5.6 kb fragment located 1.7 kb to the right of BS6. Replication from both putative origins was suppressed by rifamycin and was dependent upon dnaB. The results are discussed in relation to previous attempts to identify the first replicating fragment in germinating spores. We also discuss the possibility that B. subtilis contains two origins and suggest that either can act as the primary origin under certain conditions, or alternatively that both origins may act in concert in normal bidirectional replication, each site being required for the leading strand in each direction.
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PMID:Chromosomal initiation in Bacillus subtilis may involve two closely linked origins. 303 10

It has been found that strains carrying mutations in the dnaA gene are unusually sensitive to COU, NAL or NOV, which are known to inhibit DNA gyrase activities. The delay in the initiation of chromosome replication after COU treatment has been observed in cells with chromosomes synchronized by amino acid starvation or by temperature shift-up (dnaA46). The unusual sensitivity of growth to COU of the initiation mutant runs parallel to a higher sensitivity to the drug of the initiation of chromosome replication. The double mutant, dnaA46, cou-110 has been isolated and mutation cou-110 conferring resistance of growth, initiation and elongation of chromosome replication to COU was mapped in the gene coding for the subunit of DNA gyrase. The reduced frequency of appearance of the mutants resistant to COU, NAL, or NOV in the initiation mutant suggests that some mutations in genes coding for DNA gyrase subunits cannot coexist with the dnaA46 mutation. The possible mechanisms of the requirement of DNA gyrase for dnaA-dependent initiation of E. coli chromosome are discussed.
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PMID:Requirement of DNA gyrase for the initiation of chromosome replication in Escherichia coli K-12. 624 41

A procedure has been developed whereby the relative amounts of the topoisomers of E. coli plasmid can be determined for cells grown under a variety of conditions. Several applications of the procedure are presented. Addition of either novobiocin or oxolinic acid, two inhibitors of DNA gyrase, gives rise to positively supercoiled plasmid. A likely model for the introduction of positive supercoils, involving DNA gyrase itself, is discussed. Oxolinic acid is also shown to induce linearization of plasmid in vivo. Starvation of cells for ATP is shown to cause relaxation of plasmid. The shift of a gyrB temperature-sensitive strain to the restrictive temperature is also shown to cause plasmid relaxation. Finally, it is noted that polyamine starvation of E. coli has no detectable effect on the distribution of topoisomers.
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PMID:Positively supercoiled plasmid DNA is produced by treatment of Escherichia coli with DNA gyrase inhibitors. 630 17

Bacteriophage Mud (Casadaban and Cohen 1979) was used to bring the transcription of the gene for beta galactosidase (lacZ) under the control of the promoter of the structural gene for colicin Ib (cia(Ib)) on a derivative of the Col plasmid Col-Ib.P9. Transcription of this fusion operon was stimulated by agents which damaged cellular DNA (mitomycin C, bleomycin and colicin E2). Increased transcription of the cia-lacZ operon could be detected within 13 min of the addition of these agents. In a strain bearing the tif-1 (recA441) mutation, constitutive expression of the SOS DNA repair system at 42 degree C also increased transcription of the cia-lacZ operon. Transcription of the cia-lacZ operon was also stimulated by inhibition of DNA gyrase activity with nalidixic acid but not with novobiocin. Transitory inhibition of protein synthesis with chloramphenicol or by proline starvation of a proline auxotroph did not stimulate cia-lacZ transcription. Transcription of the cia-lacZ operon was substantially reduced in the presence of a recA mutation, but was largely unaffected by a mutation in recB affecting the RecBC DNase or by catabolite repression. Control experiments in which the production of colicin Ib was measured confirmed that the experiments with the fusion operon gave an accurate indication as to the activity of the wild type cia gene except for the effect of catabolite repression, where we observed up to 99% reduction in colicin Ib production in strains carrying mutant crp or cya alleles. The overall results confirm previous suggestions that there was considerable similarity between the regulatory systems controlling production of colicins and the repressor-dependent regulation of lambdoid prophage induction.
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PMID:Transcription regulation of colicin Ib synthesis. 646 Sep 13

The effect of plasmid pKM101 on the survival of Escherichia coli AB1157, growing in minimal medium, in the presence of a 4-quinolone DNA gyrase inhibitor was investigated. The presence of this plasmid decreased susceptibility to the quinolone ciprofloxacin, whereas mucAB genes present in a multicopy plasmid did not. The same effect of pKM101 was detected in a recA430 mutant, confirming that it was not really related to the SOS response. In contrast, when survival assays were performed under amino acid starvation conditions, pKM101 did not confer protection against ciprofloxacin. All of these results indicated that the synthesis of a product(s), different from MucAB, which was encoded by the plasmid pKM101 increased the rate of survival of the AB1157 strain in the presence of quinolone. To identify the gene(s) responsible for this phenotype, several plasmid derivatives carrying different portions of pKM101 were constructed. The 2.2-kb region containing korB, traL, korA, and traM genes was sufficient to decrease susceptibility to quinolone. This plasmidic fragment also made the AB1157 host strain grow more slowly (the Slo phenotype). Moreover, the suppression of the Slo phenotype by addition of adenine to the cultures abolished the decreased susceptibility to quinolone. These results are evidence that the protection against quinolone conferred by this region of pKM101 in strain AB1157 is a direct consequence of the slow growth rate.
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PMID:Identification of a pKM101 region which confers a slow growth rate and interferes with susceptibility to quinolone in Escherichia coli AB1157. 882 98


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