Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This work summarizes binding data that were obtained with partially purified glucocorticoid and progesterone receptors, as well as with a crude nuclear protein extract, to DNA sequences in and around hormonally regulated genes. The sequence recognition by the glucocorticoid receptor at the different defined glucocorticoid regulatory elements (GRE) is discussed and a consensus sequence formulated. A three dimensional representation gives an impression of the mode of interaction between the protein and the double helix of DNA. In the promoters of mouse mammary tomour virus (MTV) and chicken lysozyme overlapping binding sites for both, glucocorticoid and progestine-receptors are found that are responsible for the hormonal inducibility of the genes. In crude extract from rat liver nuclei, a nonhistone protein is found that specifically binds to sequences on the MTV-LTR region overlapping the GRE. The possible implication of this protein in hormonal regulation of transcription is discussed.
...
PMID:Protein-DNA interactions at steroid hormone regulated genes. 256 56

Expression of the lysozyme gene is a marker for the differentiation of macrophages, lysozyme transcription being gradually increased during maturation. We have analyzed the fine structure and function of two macrophage-specific enhancer elements of the chicken lysozyme gene (E-2.7 kb and E-0.2 kb). Both increase their activities upon LPS induction, both contain multiple binding sites for similar or identical nuclear factors and both can be divided into two functional modules. For the E-0.2 kb enhancer we found a synergistic activity of the modules to be dependent on their distance. Binding sites for nuclear proteins within enhancer E-0.2 kb overlap substantially with the previously identified progesterone/glucocorticoid receptor binding site, which is required for steroid induction of lysozyme transcription in the oviduct.
...
PMID:Cooperative interaction of chicken lysozyme enhancer sub-domains partially overlapping with a steroid receptor binding site. 276 16

The location, orientation, and structure of the hormone regulatory elements (HRE) in nine hormonally modulated genes is described. Based on analysis of the contact points between the glucocorticoid receptor (GR) and the DNA double helix within the HREs, a model for the interaction is proposed in which a dimer of the receptor in head-to-head orientation binds to the inverted symmetry element of the HRE. The relationship between the regulatory elements for glucocorticoids and progesterone in the long terminal repeat region (LTR) of mouse mammary tumor virus (MMTV), and in the promoter region of the chicken lysozyme gene, indicates that the recognition mechanism for both receptors is similar but not identical. Curiously, the hormone ligand is not an absolute requirement for the GR to bind its HRE, though it influences the kinetics of the interaction. Other possible functions of the hormone in vivo are discussed, as well as the molecular mechanism responsible for transcriptional regulation after receptor binding to the HRE.
...
PMID:Gene regulation by steroid hormones. 282 95

Glucocorticoid receptor binding sites (GRE) are often tightly clustered with other transcription factor binding sequences. Examples of this occur upstream of the genes for chicken lysozyme and human metallothionein IIA (ref. 3), in several retroviral LTRs and upstream of the rat tryptophan oxygenase (TO) gene. In the TO gene, sequences immediately upstream of a glucocorticoid receptor binding site are required for steroid induction and contain a CACCC-box identical to that found in the beta globin gene. Here we demonstrate specific binding to this TO-CACCC element and show that it will also act cooperatively with a MMTV glucocorticoid receptor binding site. The response to dexamethasone is independent of the order and relative orientation of these elements but does depend on their precise spacing. Optimal induction occurs at a periodicity of approximately 10 base pairs (bp) indicating a requirement for stereospecific alignment. Binding to the CACCC box, however, is not affected by its distance from the glucocorticoid receptor site. We conclude that the observed cooperativity is mediated by protein:protein interactions and does not depend on cooperative DNA binding.
...
PMID:Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. 283 56

The glucocorticoid receptor of rat liver recognizes nucleotide sequences near the promoter of mouse mammary tumour virus (MMTV) required for hormonal induction in gene transfer experiments. Similar nucleotide sequences have been found in the human metallothionein gene IIA and in the chicken lysozyme gene, the later induced also by oestrogen, progesterone and androgens. In microinjection experiments, deletion of only 44 base pairs (bp) of the lysozyme promoter (from -208 to -164) results in coordinated loss of progesterone and glucocorticoid-dependent gene expression. We show here that purified glucocorticoid receptor from rat liver and progesterone receptor from rabbit uterus yield similar or overlapping exonuclease III footprints in the promoter regions of MMTV and chicken lysozyme. Thus, the regulatory elements for different steroid hormones may be similar or at least share structural features.
...
PMID:Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters. 298 19

A first understanding of the molecular events on the DNA level, underlying transcriptional regulation by steroid hormones, has been approached in the last 3 years by means of protein/DNA interaction studies, using purified receptors. This work summarizes our knowledge of how purified glucocorticoid and progestine receptors interact with their cognate regulatory elements associated with polymerase II dependent genes like mouse mammary tumour virus, the genes encoding human metallothionein IIA, chicken lysozyme, human growth hormone and rabbit uteroglobin. The resulting data agree with those of functional test systems, that have been gene-transfer experiments using stable transformants or transient expression. A consensus sequence for the regulatory element of the glucocorticoid receptor could be deduced that, in its three-dimensional representation, gives an impression of the steric mode of interaction. The regulatory elements of the progestine receptor overlap in two analysed cases with those of the glucocorticoid receptor, but are not identical. Furthermore, also a polymerase I transcribed gene encoding ribosomal RNA in the mouse could be shown to contain a glucocorticoid regulatory element that is functional in in vitro transcription experiments. Finally, the latest strategies are the cloning of the glucocorticoid receptor gene and the analysis of receptor-mediated topological effects.
...
PMID:Mechanism of gene regulation by steroid hormones. 300 74

We have constructed a series of deletion mutants in the lysozyme promoter region fused to the SV40 T-antigen coding region. Regulated expression was tested after microinjection of the lysozyme deletion mutants into primary cultures of chicken oviduct cells using fluorescent antibodies against T antigen. Deletion of lysozyme gene sequences upstream of position - 164 was accompanied by loss of both progesterone- and glucocorticoid-induced expression. Using the rat liver glucocorticoid receptor for binding studies, two separate binding sites have been identified: a strong binding site that is destroyed by deletion of lysozyme sequences between positions -74 and -39 and a weaker binding site contained between positions -208 and -161 upstream of the lysozyme cap site.
...
PMID:Sequences in the promoter region of the chicken lysozyme gene required for steroid regulation and receptor binding. 672 81

Glucocorticoids inhibit translation of the lysozyme gene. This effect may be the basis of an improved method of measuring glucocorticoid responsiveness in human tissues. We have compared lysozyme synthesis in various types of white blood cells and examined the specificity of inhibitory responses to various steroid hormones. The dose-related effects of the glucococorticoid receptor antagonist RU486 on dexamethasone responses were also assessed. Glucocorticoid receptor binding in mononuclear leukocytes (HML) was characterized by homologous displacement of [3H]dexamethasone and compared with the dose-related inhibitory effect of dexamethasone on lysozyme synthesis. Lysozyme activity was measured photometrically as the ability to cause lysis of Micrococcus lysodeikticus in the medium. The greatest effect of dexamethasone was observed after 72 h of culture. Qualitatively similar effects of dexamethasone were observed on cell lysozyme content and lysozyme activity in the medium, but for convenience, activity in medium, rather than cell content, was measured in subsequent assays. Lysozyme activities in various cell types prepared from the blood of healthy volunteers were ranked as follows: polymorphonuclear cells > monocytes > mononuclear cells > lymphocytes. However, dexamethasone inhibited lysozyme synthesis to a similar degree for all types. As mononuclear cells are more conveniently prepared in greater yield compared with other cells, this HML fraction formed the basis of a method of assessing glucocorticoid responsiveness and sensitivity. Lysozyme activity from HML was not significantly affected by incubation with 1 mumol/L estradiol, progesterone, dehydroepiandrosterone, or aldosterone. Dexamethasone and cortisol at 1 mumol/L both inhibited release by 45-50%. Although RU486 when added alone partially inhibited lysozyme activity, the same concentration (1 mumol/L) antagonized glucocorticoid responses and shifted the IC50 and threshold values for the effect of dexamethasone from 1.2 nmol/L to more than 1 mumol/L and from less than 1.0 to 19 nmol/L, respectively. The equilibrium dissociation constants (Kd) for dexamethasone binding to the glucocorticoid receptor ranged from 2.8-12.5 nmol/L and were positively correlated with dexamethasone IC50 values for lysozyme synthesis (r = 0.57; P = 0.002). In conclusion, the inhibition of lysozyme synthesis by dexamethasone in human mononuclear cells is a convenient and specific method of measuring responsiveness to glucocorticoids.
...
PMID:Inhibition of lysozyme synthesis by dexamethasone in human mononuclear leukocytes: an index of glucocorticoid sensitivity. 815 14

We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes (HML) from hypertensive patients and matched normotensive volunteers. We also considered associations of these variables with plasma renin activity, aldosterone, cortisol, corticotropin, and electrolyte concentrations. We calculated binding affinity (Kd; nmol/L) and capacity (Bmax; sites/cell) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension. Glucocorticoid responsiveness of HML was evaluated as IC50 values (nmol/L) for dexamethasone and cortisol for the inhibition of lysozyme release. We measured plasma hormones by radioimmunoassay. Kd values (mean+/-SE) for cortisol in HML of hypertensive patients were higher than in control subjects (24.6+/-2.4 versus 17.5+/-1.7 nmol/L, P<.04). Binding capacity (4978+/-391 versus 4131+/-321 sites/cell), Kd values for dexamethasone (6.7+/-0.5 versus 5.7+/-0.3 nmol/L), and IC50 values for dexamethasone (3.4+/-0.3 versus 3.1+/-0.2 nmol/L) and cortisol (12.2+/-1.6 versus 9.5+/-0.3 nmol/L) were not significantly different. Patients with renin values less than 0.13 ng angiotensin I/L per second were markedly less sensitive to cortisol than those with higher values. Both Kd (30.3+/-2.5 versus 19.2+/-2.4 nmol/L) and IC50 values (15.5+/-1.8 versus 8.9+/-1.2 nmol/L) for cortisol were significantly higher in patients with lower renin values (P<.03). Other variables, including plasma hormone and electrolyte values and binding characteristics for dexamethasone, were not different. These data suggest that cortisol binding to glucocorticoid receptor is slightly impaired in patients with essential hypertension. In vivo, this could lead to inappropriate binding of cortisol to mineralocorticoid receptors. Hence, decreased sensitivity to cortisol is associated with renin suppression. This hypothesis is supported by evidence of hypertension and low renin activity, which others have described in patients with primary glucocorticoid resistance due to mutations of the glucocorticoid receptor.
...
PMID:Impaired cortisol binding to glucocorticoid receptors in hypertensive patients. 936 87

Genetic variation of the glucocorticoid receptor (GR) locus is associated with differences in blood pressure. To define the intermediate phenotypes associated with this variation, we investigated the biochemical and clinical significance of a BclI restriction fragment length polymorphism of the GR locus in 64 normal male volunteers. Blood samples were genotyped as either AA (homozygous large allele; n = 6), Aa (heterozygous; n = 51), or aa (homozygous small allele, n = 7). Four primary glucocorticoid variables were measured including GR binding characteristics and glucocorticoid-sensitive lysozyme release of leukocytes in vitro and the blanching response of forearm skin to budesonide. A large number of secondary variables (urinary and plasma steroid measurements, blood pressure and indices of body fat metabolism, and routine biochemical and hematological measurements) were also considered. In vivo sensitivity to budesonide was greater in AA than aa individuals (mean +/- SE EC50 values: 13 +/- 5 and 42 +/- 10 ng; P < 0.01). In contrast, leukocytes of AA subjects tended to have lower affinity and reduced sensitivity for dexamethasone, although these effects were not statistically significant. Based on urinary steroid measurements, 11 beta-hydroxysteroid dehydrogenase activity [ratio of tetrahydrocortisol (THF) to tetrahydrocortisone (THE) metabolites] was not affected by genotype. The relative activities of 5 alpha- and 5 beta-reductase activity (allo-THF/THF + THE) appeared lower in AA than aa subjects (0.22 +/- 0.04 cf. 0.33 +/- 0.06; P < 0.005) but were not judged to be significantly different when corrected for multiple comparisons. Single and multivariate analyses were carried out to determine which variables influence GR binding characteristics and glucocorticoid responsiveness and to see whether cardiovascular risk factors (blood pressure and body fat) were influenced by glucocorticoid-dependent functions. Only 15-20% of the variations in the dissociation constant (Kd) and maximum binding capacity (Bmax) were influenced by other variables; plasma cholesterol was the most important for affinity and plasma sodium concentration for binding capacity. Multivariate analysis showed that several factors including GR genotype and urinary cortisol account for 10% of the variation of in vivo responses to glucocorticoid hormones; plasma calcium concentration was the only variable that contributed to in vitro sensitivity of leukocytes to dexamethasone. Glucocorticoid-dependent responses were of negligible importance in determining blood pressure or percentage body fat within the narrow physiological ranges of the present study. We conclude that GR genotype affects steroid sensitivity in a tissue-specific manner because of altered GR function or possibly because of linkage to a locus that controls hormone access to the receptor by influencing steroid metabolism.
...
PMID:Glucocorticoid receptor polymorphism, skin vasoconstriction, and other metabolic intermediate phenotypes in normal human subjects. 962 6


1 2 3 Next >>

---