Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a dynamic interaction between a drug's pharmacological effects and the behavioral context in which it is administered. The present study evaluated the influence of behavioral processes on the development of tolerance and cross-tolerance to the rate-decreasing effects of chlordiazepoxide in rats. Sprague-Dawley rats responded under a fixed-ratio 30 schedule of food delivery. Different groups of rats received 18 mg/kg/day of chlordiazepoxide either before (PRE, n = 8) or after (POST, n = 10) daily experimental sessions for 8 weeks. Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration. Cumulative dose-response curves for midazolam, FG 7142 (N-methyl-beta-carboline-3-carboxamide) flumazenil, pentobarbital, caffeine, morphine and d-amphetamine were determined before, during and 4.5 to 5 months after chronic chlordiazepoxide administration. Group PRE developed tolerance to chlordiazepoxide, whereas group POST did not develop tolerance. Although cross-tolerance developed to midazolam in both groups, it was greater in group PRE. Both groups showed comparable sensitization to FG7142 and neither group showed a significant change in sensitivity to any of the other drugs. Biochemical studies of gamma-aminobutyric acid (GABA)-related functioning in groups of rats that received chronic chlordiazepoxide administration either before (BIO-PRE, n = 6) or after (BIO-POST, n = 6) daily sessions found that GABA-stimulated 36Cl-uptake increased in both cortical and cerebellar preparations. However, GABA sensitivity in cerebellar tissue was significantly lower in group BIO-PRE compared with group BIO-POST. Thus, behavioral tolerance to chlordiazepoxide was associated with both pharmacological and biochemical effects, which suggests a relationship between behavioral tolerance to benzodiazepines and changes in the functional state of the GABA-benzodiazepine receptor complex.
J Pharmacol Exp Ther 1993 Dec
PMID:Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and biochemical selectivity. 826 95

Using a DNA-protein binding assay, we have previously identified and characterized a UV-damaged DNA recognition protein (UVDRP) from HeLa cells [(1991) Nucleic Acids Res. 19, 6413-6418]. In this report, the photoreactivating activity of UVDRP from the yeast, Saccharomyces cerevisiae, and HeLa cells was investigated. Although yeast and human cells are evolutionarily different from each other, both UVDRPs were conserved in the sense of their biochemical characteristics except that the yeast UVDRP also exhibited an enzymatic photoreactivating activity. A mammalian expression vector plasmid DNA carrying the bacterial chloramphenicol acetyltransferase (CAT) gene was UV irradiated in vitro followed immediately by exposure to photoreactivating light, and its transient expression in repair-deficient xeroderma pigmentosum (XP) cells was investigated. More than 80% of the CAT activity was inhibited by UV irradiation, which was partially restored (> 60%) by a partially purified yeast photolyase. In contrast, HeLa cell extracts did not express a photoreactivatable recovery from UV-induced inhibition of the CAT activity tested in the same system. This study has demonstrated the potential use of the DNA-mobility shift assay to investigate enzymatic photoreactivation, and has indicated the absence of the repair mechanism in human cells.
FEBS Lett 1993 Dec 28
PMID:Lack of DNA enzymatic photoreactivation in HeLa cell-free extracts. 828 3

In Escherichia coli, the light-dependent repair of pyrimidine dimers in UV-irradiated DNA is now accepted as being due to enzymatic photoreactivation (PR) by a 50 kDa enzyme, photolyase (EC 4.1.99.3). The gene for this enzyme has been mapped at 16.2 min and designated phr. This gene was earlier described as phrB, another locus phrA having been proposed in association with PR. The relevance of the putative phrA gene has now been placed in doubt. The recent report of the discovery of a photoreactivating enzyme in Drosophila melanogaster, which specifically repairs pyrimidine (6-4) pyrimidone photoproducts ([6-4] photoproducts), and that E. coli does possess a protein with specific affinity for the (6-4) photoproduct, has cast new light on the prospective role of phrA in PR. We have determined the nucleotide sequence of the putative phrA gene, which suggests it codes for a protein of 38 kDa. When the putative phrA gene was cloned into an expression vector and transformed into a phrA phrB mutant of E. coli, a level of photorepair was observed, which could correspond to repair of (6-4) photoproducts.
Photochem Photobiol 1993 Dec
PMID:Photoreactivation in a phrB mutant of Escherichia coli K-12: evidence for the role of a second protein in photorepair. 831 5

DNA photolyase is a light-dependent DNA repair enzyme. It binds to cyclobutane pyrimidine dimers <PyrPyr> in DNA and upon excitation with a blue light photon splits the cyclobutane ring and restores the pyrimidines to native forms. The enzyme is specific for pyrimidine dimers, and it is not known to catalyze any other reaction either in ground or in excited state. However, when photolyase binds to <PyrPyr> but cannot catalyze repair because of lack of photoreactivating light, it still aids DNA repair by stimulating the nucleotide excision repair system. Recently, it was found that yeast photolyase binds to other lesions in DNA. In particular, the binding to cisplatin damaged DNA was highly specific. However, in vivo experiments revealed that this binding, in contrast to <PyrPyr> binding, did not stimulate but actually inhibited the removal of cisplatin damage by excision repair and hence photolyase sensitized cells to killing by cisplatin. In the present study, it is demonstrated that Escherichia coli DNA photolyase binds specifically to cisplatin 1,2-d(GpG) intrastrand cross-link and stimulates the removal of the lesion by E. coli excision nuclease in vitro. In agreement with the in vitro data, in vivo experiments revealed that photolyase makes cells more resistant to cisplatin killing.
Biochemistry 1995 Dec 12
PMID:The other function of DNA photolyase: stimulation of excision repair of chemical damage to DNA. 851 44

Of 310 random cosmid clones, 216 were positive for PRE-1 sequences by Southern hybridization. Thirty nine sub-fragments positive for the PRE-1 sequences were cloned from independent cosmid clones, and sequenced, with 17 complete PRE-1 elements found. Seven PRE-1 loci were amplified by polymerase chain reaction using genomic DNA of 12 unrelated pigs as template. The amplified fragments were then subjected to an analysis of single strand conformation polymorphism, with all the loci being polymorphic.
Anim Genet 1995 Dec
PMID:Survey on swine SINEs (PRE-1) as candidates for SSCP markers in genetic linkage analysis. 857 62

In order to better understand the biochemical mechanisms of DNA metabolism in chloroplasts, repair of UV induced plastome damage in vivo was determined by exposure of soybean suspension cells to UV light and subsequent quantitation of the damage remaining in nuclear and chloroplast encoded genes with time by quantitative polymerase chain reaction (QPCR). The kinetics of damage repair in the nuclear rbcS gene suggest that photoreactivation and dark mechanisms are active, while for the plastome encoded psbA gene only a light-dependent repair process was detected which is considerably slower than would be expected for photolyase-mediated photoreactivation.
Plant Mol Biol 1995 Dec
PMID:Repair mechanisms of UV-induced DNA damage in soybean chloroplasts. 861 23

The rates of increase in O2 uptake (VO2) after step changes in work rate from 25 W to 60% of pretraining peak VO2 (VO2 peak) were measured at various times during an endurance training program (2 h/day at 60% pretraining VO2 peak). Seven untrained males [23 +/- 1 (SE) yr] performed a series of repeated step changes in work rate before training (PRE) and after 4 days (4D), 9 days (9D), and 30 days (30D) of training. VO2 kinetic responses were determined from breath-by-breath data averaged across four repetitions and analyzed using a two-component exponential model. Mean response time (time taken to reach 63% of steady-state VO2) was faster (P < 0.01) than PRE (38.1 +/- 2.6 s) at both 4D (34.9 +/- 2.4 s) and 9D (32.5 +/- 1.8 s) and was faster (P < 0.01) at 30D than at all other times (28.3 +/- 1.0 s). Blood lactate concentrations (after 6 min of cycling) were also lower at 4D and 9D than PRE (P < 0.01) and were lower at 30D than at all other times (P < 0.01). VO2 peak was unchanged from PRE (3.52 +/- 0.20 l/min) at 8D (3.55 +/- 0.20 l/min) but was increased (P < 0.01) at 30D (3.89 +/- 0.18 l/min). Muscle oxidative capacity (maximal citrate synthase activity) was not significantly increased until 30D (P < 0.01). It is concluded that at least part of the acceleration of whole body VO2 kinetics with endurance training is a rapid phenomenon, occurring before changes in VO2 peak and/or muscle oxidative potential.
J Appl Physiol (1985) 1995 Dec
PMID:Progressive effect of endurance training on VO2 kinetics at the onset of submaximal exercise. 884 53

The cyclobutane pyrimidine dimer (CPD) photolyase in fish cells is known to be regulated by environmental factors, such as light, hydrogen peroxide and growth inhibition. The induction of CPD photolyase by light in cultured goldfish cells was dependent on the wavelength of the light, and UVA and blue light had high inductive activity. The spectrum for CPD photolyase activity was different from that for the induction. Treatment with blue or yellow light for a short time, which did not induce any CPD photolyase, induced high CPD photolyase activity in the presence of the photosensitizers, TPPS (monosulfonated meso-tetraphenyl porphine) and ALPS (aluminum phthalocyanine tetrasulfonate), respectively. These results suggest that the induction of CPD photolyase might be triggered by active oxygen produced by light and cellular photosensitizers. We also found that immediately after treatment with UVA, blue light or a photosensitizer in combination with light, cellular attachment to the substratum was enhanced, as was the CPD photolyase activity. Pretreatment with a flavonoid, quercetin, inhibited both photoinduction of CPD photolyase and enhancement of cellular attachment. Vitamin E inhibited only photoinduction of CPD photolyase activity. Treatment with H7, a strong inhibitor for protein kinase C, after light treatment inhibited photoinduction of CPD photolyase activity, but an analogue of H7, Ha1004, which is a weak inhibitor of protein kinase C, did not have such an effect.
Photochem Photobiol 1996 Dec
PMID:Induction of cyclobutane pyrimidine dimer photolyase in cultured fish cells by UVA and blue light. 897 35

This experiment was designed to examine the hypothesis that perinatal manipulation of gonadal or adrenal steroids can alter the subsequent expression of juvenile parental (alloparenting) and affiliative behavior in prairie voles (Microtus ochrogaster). Corticosterone (PRECORT), testosterone (PRE-TP), or oil injections (PRESES) were given on Prenatal Days 12-20 or on Postnatal Days 1-6 (CORT6, TP6, or SES6, respectively). Alloparenting was reduced significantly in females in the CORT6 group and in males in the TP6 group. Sibling affiliative preferences were increased significantly in PRE-TP females and stranger preferences were increased in TP6 and CORT6 females. The results suggest timing is a critical factor determining whether hormones have a facilitative or inhibitory effect on alloparental and affiliative behavior in prairie voles. In this species, corticosterone and testosterone have similar organizational effects on affiliative behavior in females. Alloparental behavior is inhibited by postnatal corticosterone administration in females and by postnatal testosterone administration in males, whereas prenatal steroid administration had no significant effect on alloparenting in either gender.
Horm Behav 1996 Dec
PMID:Perinatal steroid treatments alter alloparental and affiliative behavior in prairie voles. 904 81

The (6-4) photolyase catalyzes the photoreversal of the (6-4) dipyrimidine photoproducts induced in DNA by ultraviolet light. Using the cloned Drosophila melanogaster (6-4) photolyase gene, we overproduced and purified the recombinant enzyme. The binding and catalytic properties of the enzyme were investigated using natural substrates, T[6-4]T and T[6-4]C, and the Dewar isomer of (6-4) photoproduct and substrate analogs s5T[6-4]T/thietane, mes5T[6-4]T, and the N-methyl-3'T thietane analog of the oxetane intermediate. The enzyme binds to the natural substrates and to mes5T[6-4]T with high affinity (KD approximately 10(-9)-10(-10) M) and produces a DNase I footprint of about 20 base pairs around the photolesion. Several lines of evidence suggest that upon binding by the enzyme, the photoproduct flips out of the duplex. Of the four substrates that bind with high affinity to the enzyme, T[6-4]T and T[6-4]C are repaired with relatively high quantum yields compared with the Dewar isomer and the mes5T[6-4]T which are repaired with 300-400-fold lower quantum yield than the former two photoproducts. Reduction of the FAD cofactor with dithionite increases the quantum yield of repair. Taken together, the data are consistent with photoinduced electron transfer from reduced FAD to substrate, in a manner analogous to the cyclobutane pyrimidine dimer photolyase.
J Biol Chem 1997 Dec 19
PMID:Reaction mechanism of (6-4) photolyase. 940 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>