Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rfb (O antigen) gene cluster of group C2 Salmonella differs from that of group B in a central region of 12.4 kb: we report the sequencing of this region of strain M67 (group C2) and a subsequent comparison with the central region of strain LT2 (group B). We find a block of seven open reading frames unique to group C2 which encode the O antigen polymerase (rfc) and the transferases responsible for assembly of the group C2 O antigen. The remaining rfb genes are common to strains M67 and LT2, but rfbJ (CDP-abequose synthase) and rfbM and rfbK (GDP-mannose synthesis), which are immediately adjacent to the central region, are highly divergent. All these genes have a low G+C content and appear to have been recent additions to Salmonella enterica. We discuss the evolutionary significance of the arrangement and divergence of the genes in the polymorphism of the rfb cluster.
Mol Microbiol 1992 May
PMID:Molecular analysis of the rfb gene cluster of Salmonella serovar muenchen (strain M67): the genetic basis of the polymorphism between groups C2 and B. 137 20

Phosphatidylglycerolphosphate synthase (PGPS; CDP-diacylglycerol glycerol 3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) catalyzes the first step in the synthesis of cardiolipin, an acidic phospholipid found in the mitochondrial inner membrane. In the yeast Saccharomyces cerevisiae, PGPS expression is coordinately regulated with general phospholipid synthesis and is repressed when cells are grown in the presence of the phospholipid precursor inositol (M. L. Greenberg, S. Hubbell, and C. Lam, Mol. Cell. Biol. 8:4773-4779, 1988). In this study, we examined the regulation of PGPS in growth conditions affecting mitochondrial development (carbon source, growth stage, and oxygen availability) and in strains with genetic lesions affecting mitochondrial function. PGPS derepressed two- to threefold when cells were grown in a nonfermentable carbon source (glycerol-ethanol), and this derepression was independent of the presence of inositol. PGPS derepressed two- to fourfold as cells entered the stationary phase of growth. Stationary-phase derepression occurred in both glucose- and glycerol-ethanol-grown cells and was slightly greater in cells grown in the presence of inositol and choline. PGPS expression in mitochondria was not affected when cells were grown in the absence of oxygen. In mutants lacking mitochondrial DNA [( rho0] mutants), PGPS activity was 30 to 70% less than in isogenic [rho+] strains. PGPS activity in [rho0] strains was subject to inositol-mediated repression. PGPS activity in [rho0] cell extracts was derepressed twofold as the [rho0] cells entered the stationary phase of growth. No growth phase derepression was observed in mitochondrial extracts of the [rho0] cells. Relative cardiolipin content increased in glycerol-ethanol-grown cells but was not affected by growth stage or by growth in the presence of the phospholipid precursors inositol and choline. These results demonstrate that (i) PGPS expression is regulated by factors affecting mitochondrial development; (ii) regulation of PGPS by these factors is independent of cross-pathway control; and (iii) PGPS expression is never fully repressed, even during anaerobic growth.
 ...
PMID:Regulation of phosphatidylglycerolphosphate synthase in Saccharomyces cerevisiae by factors affecting mitochondrial development. 165 99

Avian skin fibroblasts were isolated, cultured and incubated with [3H]proline for 24 h. The cells exported radiolabeled collagenase-digestible (CDP) and non-collagenase-digestible (NCDP) proteins into the medium. Human, bovine and avian growth hormone (GH) as well as insulin-like growth factor I (IGF-I) attenuated the appearance of [3H]CDP in the medium without affecting [3H]NCDP. The appearance of [3H]CDP was not affected by prolactin. The effects of GH and IGF-I were enhanced by increasing concentrations of fetal calf serum (FCS). A synergism was observed between GH and IGF-I in their effect on CDP. Each peptide, at an ineffective concentration, increased the sensitivity of the cells to the other peptide. Collagenase activity in the medium was enhanced by IGF-I, but not modified by GH, FCS, or by their interaction with IGF-I. GH and IGF-I inhibition of type I procollagen gene expression was demonstrated with the aid of probes containing sequences corresponding to the mRNAs for avian alpha I and alpha II chains. The results suggest that GH and IGF-I cooperate in regulating collagen synthesis, but collagen degradation is affected by IGF-I and not by GH.
Mol Cell Endocrinol 1991 Sep
PMID:Growth hormone and insulin-like growth factor I regulate collagen gene expression and extracellular collagen in cultures of avian skin fibroblasts. 165 42

The influence of an increased temperature (39 degrees C) on a denaturation of 50 kDa-fragment of myosin subfragment 1 was studied in the presence of different nucleoside triphosphates (NTP) and nucleoside diphosphates (NDP). The degree of the denaturation was appreciated evaluated from its trypsinolysis depth. According to their protective influence NTP and NDP were shown to arrange in lines ATP greater than or equal to CTP greater than UTP greater than GTP and ADP greater than GDP greater than CDP greater than UDP, correspondingly. The results received and the literature data allow to suggest that there are at least two states of ATPase site hydrophobic pocket, one of which in responsible for sharp ATPase reaction slowing-down on the stage of macroergic bonding splitting.
Mol Biol (Mosk)
PMID:[Functionally different states of the "hydrophobic pocket" of the myosin ATPase center]. 183 76

The molecular specificity of phosphatidylcholine (PC) synthesis by the de novo pathway in postmortem samples of human fetal lung (15 to 20 wk of gestation) was determined from the incorporation pattern in isolated microsomal preparations of CDP:[14C]choline into individual molecular species of PC. These analyses are based on the assumption that the molecular species composition of the pool of endogenous diacylglycerol used for PC synthesis by isolated microsomes reflects that of the authentic pool of diacylglycerol converted to PC by intact cells. Comparison of this microsomal incorporation pattern of radiolabel into PC with tissue PC composition suggested that even at this early stage of gestation 50% of lung dipalmitoyl PC was derived from synthesis de novo, with the remainder coming from acyl remodeling mechanisms. Analysis of PC synthesis de novo by organ cultures of human fetal lung showed that these acyl remodeling mechanisms were lost in culture. Despite evidence for differentiation of type II alveolar epithelial cells in culture, equilibrium labeling of PC with [14C]choline over 18 h resulted in a progressive decline in fractional incorporation into dipalmitoyl PC with time in culture. By 4 days in culture, this value was no different from the fractional incorporation of CDP:[14C]choline into microsomal PC in vitro over 3 h. The pattern of PC synthesized was not altered when total PC synthesis was stimulated by exposure of cultures to dexamethasone and tri-iodothyronine but was readily manipulated by exposure to exogenous fatty acids. These results demonstrate for the first time the activity of PC acyl remodeling mechanisms in human fetal lung, well before the initiation of surfactant production.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Oct
PMID:Mechanisms of phosphatidylcholine acyl remodeling by human fetal lung. 191 Aug 21

In the last few years it has become possible in the liver to isolate lymphocytes from inflammatory infiltrates and to culture them in vitro. Most of the lymphocyte clones obtained are CD 8+ cytotoxic cells, but interactions between these lymphocytes and hepatocytes in primary culture have not been analysed previously. In this study, cloned human T lymphocytes from liver biopsies and from the peripheral blood of patients with chronic hepatitis B or primary biliary cirrhosis, after phenotypical and functional characterization into CD 8+ or CD 4+ cytotoxic lymphocytes, were activated in an antigen-independent fashion by adding either anti CD 3 or anti CD 2/R-3 monoclonal antibodies to the cell suspension. The activated cells were then coincubated with rat hepatocytes in primary culture. The killing capacity of the activated lymphocytes was monitored by light and electron microscopy and by measurement of lactic dehydrogenase (LDH)-release into the culture medium. It was found that cytotoxic CD 8+, but not CD 4+ helper lymphocytes very effectively killed hepatocytes. The killing effect was dependent on the time of cocultivation and on effector-target (E/T) ratio. Total breakdown of the hepatocyte monolayer was achieved after 10-20 h coculture and at an E/T ratio of 10 to 1. As LDH-release in the culture medium reached about 80% of the total LDH-content, most of the hepatocytes were lysed by activated lymphocytes. Cytotoxic activity of clones obtained from different biopsies was comparable with that of clones from peripheral blood. Hepatocytes in primary culture seem to be very sensitive to the killing capacity of activated cytotoxic lymphocytes.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Lymphocytes from hepatic inflammatory infiltrate kill rat hepatocytes in primary culture. Comparison with peripheral blood lymphocytes. 198 May 56

Binding of TRH to specific cell surface receptors on clonal GH4C1 cells is followed within 10 min by receptor sequestration and over 24 h by receptor down-regulation. These experiments were designed to determine if TRH-activated second messenger systems are responsible for changes in receptor localization or number. BAY K8644 and A23187, which increase intracellular calcium, alone or together with 12-O-tetradecanoyl phorbol acetate (TPA), which activates protein kinase C, did not appear to internalize TRH receptors. Drug treatment did not alter the rate of [3H]MeTRH association or internalization, determined by resistance to an acid/salt wash, or the amount of [3H]MeTRH able to bind at 0 C, where only surface receptors are accessible. TPA (0-100 nM) alone or in combination with BAY K8644 or A23187, also failed to change receptor number or affinity after 48 h when TRH caused a 75% decrease in the density of specific binding sites. Chlordiazepoxide has been reported antagonize TRH binding and TRH-induced phospholipid breakdown. Chlordiazepoxide shifted the dose-response curves for TRH stimulation of PRL release and synthesis to the right, and did not change PRL release alone. The affinity of receptors for chlordiazepoxide was not affected by a nonhydrolyzable analog of GTP whereas affinity for TRH was decreased; these properties are consistent with the classification of chlordiazepoxide as a competitive antagonist. Several experiments tested whether chlordiazepoxide would cause receptor internalization and down-regulation. Chlordiazepoxide did not appear to internalize TRH receptors, because TRH-binding sites became available rapidly and at the same rate after they had been saturated with chlordiazepoxide at 0 or 37 C.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Sep
PMID:Pituitary thyrotropin-releasing hormone (TRH) receptors: effects of TRH, drugs mimicking TRH action, and chlordiazepoxide. 248 18

In this study the effect of myocardial ischaemia was evaluated on two aspects of phospholipid metabolism: (i) the de novo synthesis of myocardial phospholipids, as indicated by the incorporation of (methyl-3H) choline and (ii) the incorporation of radiolabelled long chain fatty acids into tissue phospholipids. Two models of ischaemia were used namely normothermic ischaemic arrest and hypoxic, low-flow perfusion of the isolated rat heart. The results showed that within 10 min, hypoxic low-flow perfusion significantly inhibited the incorporation rate of (methyl-3H) choline into tissue phospholipids. Since the tissue choline content remained unaltered under these conditions, the results suggested that the de novo synthesis of phosphatidylcholine is very susceptible to ischaemic damage. Inhibition of (methyl-3H) choline incorporation into tissue phospholipids appeared to be due to both a reduction in choline uptake and specific inhibition of the CDP pathway. Perfusion with glucose (10 mM) as substrate completely abolished the ischaemia-induced reduction in (methyl-3H) choline incorporation, indicating that glycolytically produced ATP played an important role in phosphatidylcholine biosynthesis. In contrast to these results, myocardial ischaemia stimulated the incorporation of long-chain saturated and unsaturated fatty acids into tissue phospholipids. In summary, the results obtained showed that myocardial ischaemia profoundly affected phospholipid metabolism which, in turn, might contribute to membrane damage.
J Mol Cell Cardiol 1989 Feb
PMID:Phosphatidylcholine biosynthesis in myocardial ischaemia. 254 85

gamma-Aminobutyric acidA (GABAA) receptors on chick ciliary ganglion neurons can be modulated by benzodiazepines and identified by radiolabeled benzodiazepine binding. Enhancement of submaximal GABA responses by benzodiazepines was demonstrated using a multibarrel pipette to construct complete benzodiazepine dose-response curves for single cells in culture. EC50 values of 22 +/- 5 nM, 1.1 +/- 0.3 microM, and 4.6 +/- 0.5 microM were obtained for flunitrazepam, clonazepam, and chlordiazepoxide, respectively. Chlordiazepoxide shifted the GABA dose-response curve to lower GABA concentrations without increasing the maximal response to GABA, demonstrating that benzodiazepines enhance the GABA response by increasing the receptor affinity for GABA. The imidazodiazepine Ro15-1788 potentiated the GABA response with an EC50 of 250 +/- 70 nM, and Ro5-4864 (chlorodiazepam) partially blocked the GABA response both in the presence and absence of chlordiazepoxide. Scatchard analysis of data from binding studies with [3H]flunitrazepam to ganglion membrane homogenates was consistent with the presence of a single class of high affinity sites with a KD of 34 +/- 6 nM and a Bmax of 145 +/- 26 fmol/mg of protein. Several lines of evidence indicated that the sites were associated with GABAA receptors. The KD of [3H]flunitrazepam binding was similar to the EC50 for flunitrazepam modulation of the GABA response. The level of [3H]flunitrazepam binding was enhanced approximately 50% over control levels by GABA. The binding was decreased both by clonazepam and by Ro5-4864 at concentrations similar to those required for the compounds to modulate the GABA response. These studies demonstrate that ciliary ganglion GABAA receptors are similar in major respects to GABAA receptors in the central nervous system but may differ in minor pharmacological properties.
Mol Pharmacol 1988 Aug
PMID:Benzodiazepine interactions with GABAA receptors on chick ciliary ganglion neurons. 284 52

TRH receptors have been solubilized from GH4C1 cells using the plant glycoside digitonin. Solubilized receptors retain the principal binding characteristics exhibited by the TRH receptor in intact pituitary cells and their membranes. The binding of the methylhistidyl derivative of TRH [( 3H]MeTRH) attained equilibrium within 2-3 h at 4 C, and it was reversible, dissociating with a t1/2 of 7 h. Analysis of [3H]MeTRH binding to soluble receptors at 4 C yielded a dissociation constant (Kd) of 3.8 nM and a total binding capacity (Bmax) of 3.9 pmol/mg protein. Peptides known to interact with non-TRH receptors on GH cells failed to interfere with the binding of [3H]MeTRH, indicating that the TRH binding was specific. Chlordiazepoxide, a competitive antagonist for TRH action in GH cells, inhibited TRH binding to soluble receptors with an IC50 of 11 microM. When [3H]MeTRH was bound to membranes and the membrane proteins were then solubilized, we found enhanced dissociation of the prebound [3H]MeTRH from its solubilized receptor by guanyl nucleotides. Maximal enhancement of [3H]MeTRH dissociation by 10 microM GTP gamma S occurred within about 45 min at 22 C. GTP gamma S, GTP, GDP beta S, and GDP were all effectors of [3H]MeTRH dissociation, exhibiting EC50s in the range of 14-450 nM. The rank order of potency of the tested nucleotides was GTP gamma S greater than GTP congruent to GDP beta S greater than GDP much greater than ATP gamma S greater than GMP. We conclude that TRH receptors have been solubilized from GH cells with digitonin and retain the binding characteristics of TRH receptors in intact pituitary cells. Furthermore, prebinding [3H]MeTRH to GH4C1 cell membranes results in the solubilization of a complex in which the TRH receptor is linked functionally to a GTP binding protein.
Mol Endocrinol 1987 Dec
PMID:Solubilization of receptors for thyrotropin-releasing hormone from GH4C1 rat pituitary cells: demonstration of guanyl nucleotide sensitivity. 285 5


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