Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Interplay”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1992

The interplay between basicity, conformation, and enzymatic reduction in biliverdins.

Biliverdins with extended conformations are reduced by biliverdin reductase (BvR) at higher rates than biliverdins with helical conformations. To find out the molecular basis for this important feature of BvR mechanism, helical and extended biliverdins were titrated for their acid-base equilibria in a protic solvent (methanol). It was found that the basicity of biliverdins increases with the stretching of the conformation. Biliverdin IX gamma (all-syn) has a pKa = 3.6; 5,10,15-syn,syn,anti-biliverdin has a pKa = 3.7; 5,10,15-syn,anti,syn-biliverdin has a pKa = 6.1; 5,10,15-syn,anti,anti-biliverdin has a pKa = 6.4; and 5,10,15-all-anti-biliverdin has a pKa = 7.9. The increase in basicity with progressive stretching of conformations closely parallels the increase in the reduction rates by BvR. A biliverdin constrained by a four carbon chain to a helical conformation and which is a very weak base (pKa = 0.4) is not reduced by BvR. Nucleophilic additions of 2-mercaptoethanol at the C10 in biliverdins closely parallel their basicities, as can be expected if the formation of a positive mesomeric species at C10 is linked to the basicity (i.e., the ease of protonation) of the N23 on the pyrrolenine ring.

Biliverdine↗
PubMed1995

Induction mechanisms of cytochrome P450 2E1 in liver: interplay between ethanol treatment and starvation.

Chronic ethanol exposure causes marked induction of the ethanol-inducible cytochrome P450 (CYP) 2E1 isozyme in the centrilobular liver region, where alcoholic damage commonly is initiated. In contrast to most other CYP forms, which are ligand-activated at the transcriptional level, ethanol induction of CYP2E1 has been found to be post-translational. However, transcriptional activation of the CYP2E1 gene was recently described in fed animals maintained at very high ethanol levels. To further evaluate mechanisms of ethanol-mediated CYP2E1 induction we compared the effect of short-term heavy-ethanol treatment and fasting on CYP2E1 mRNA, protein and catalytic activity. High blood-ethanol levels (20-70 mM) were maintained for 3 days by regular alcohol intubations to fed or fasted rats. During this period, the amount of liver CYP2E1 apoprotein increased a maximum of 20-fold and catalytic activity 16-fold, both in fed and fasted animals, whereas starvation alone caused only a 4- to 5-fold increase. By comparison, the amount of CYP2E1 mRNA, as assayed both by Northern blot and slot blot, was significantly increased (5- to 6-fold) by ethanol only in fasted rats; this increase was smaller than that observed after fasting alone (8- to 9-fold). Analysis of cell lysates isolated from the periportal and perivenous region revealed that the increase in CYP2E1 mRNA by fasting occurred in the perivenous region. Thus no evidence was obtained for an increased pretranslational CYP2E1 gene expression as a consequence of the continuous presence of ethanol at intoxicating levels for 3 days. CYP2E1 mRNA elevation seems to be strongly associated with starvation while alcohol treatment increases the amount of enzyme, primarily by ligand-dependent stabilization of the synthesized protein. Our results indicate that transcriptional activation of CYP2E1 requires the long-term presence of highly intoxicating ethanol levels. It is conceivable that such activation occurs via indirect physiological responses related to those triggered by starvation.

Animals↗
PubMed1992

Interplay between proliferation and differentiation within the myogenic lineage.

In muscle cells, as in a variety of cell types, proliferation and differentiation are mutually exclusive events controlled by a balance of opposing cellular signals. Members of the MyoD family of muscle-specific helix-loop-helix proteins which, in collaboration with ubiquitous factors, activate muscle differentiation and inhibit cell proliferation function at the nexus of the cellular circuits that control proliferation and differentiation of muscle cells. The activities of these myogenic regulators are negatively regulated by peptide growth factors and activated oncogenes whose products transmit growth signals from the membrane to the nucleus. Recent studies have revealed multiple mechanisms through which intracellular growth factor signals may interfere with the functions of the myogenic regulators. When expressed at high levels, members of the MyoD family can override mitogenic signals and can cause growth arrest independent of their effects on differentiation. The ability of these myogenic regulators to inhibit proliferation of normal as well as transformed cells from multiple lineages suggests that they interact with conserved components of the cellular machinery involved in cell cycle progression and that similar types of regulatory factors participate in differentiation and cell cycle control in diverse cell types.

Animals↗
PubMed1996

Growth inhibition by Abl requires an interplay of its SH2 and tyrosine kinase domains.

Overexpression of c-Abl tyrosine kinase can be growth inhibitory in certain fibroblast cell lines. Using a series of conditional chimeras between Abl and Src, we have now further dissected the Abl protein to determine which domains are required for this function. We found that growth inhibition, unlike transformation by oncogenic forms of Abl, is dependent on the presence of the cognate SH2 and tyrosine kinase domains. Since growth inhibition correlates with low tyrosine kinase activity, it may involve highly specific interactions of target proteins with both domains without the processivity of phosphorylation associated with oncogenic Abl.

3T3 Cells↗
PubMed1987

The interplay of DNA-binding proteins on the promoter of the mouse albumin gene.

The promoter of the mouse albumin gene contains at least six binding sites for specific DNA-binding proteins (A to F). Four of these sites (A, D, E, and F) can be occupied by transcription factors that are considerably enriched in liver nuclei, as compared to spleen or brain nuclei. These factors consist of a heat-stable protein that fills sites A, D, and F, and a member of a family of nuclear factor I (NF-I) related proteins that occupies site E. Site C binds a protein that is equally abundant in liver, brain, and spleen nuclei. Occupancy of this site and the binding of the heat-stable factor to the immediately adjacent site D appear to be mutually exclusive. However, both of these competing binding sites are required for maximal in vitro transcription.

Albumins↗
PubMed1991

In vivo footprinting of rat TAT gene: dynamic interplay between the glucocorticoid receptor and a liver-specific factor.

HNF5, a liver-specific DNA-binding protein, interacts with DNA in a manner that allows DNAase I cleavage in the middle of its recognition sequence. Using this property we have identified in vivo HNF5 bound to its sites within two glucocorticoid-responsive units of the rat tyrosine aminotransferase (TAT) gene. One HNF5-binding site is also a glucocorticoid receptor-binding site; glucocorticoid-dependent HNF5 binding could be detected at this site even though it is incompatible with glucocorticoid receptor binding. HNF5 binds within 10 min of hormone addition, indicating that it participates in transcriptional activation. In the TAT gene glucocorticoid-dependent HNF5 binding occurs where there is glucocorticoid-dependent disruption of nucleosomal structure; constitutive binding occurs in constitutively disrupted regions. These results suggest a hit-and-run mechanism of transcriptional activation by glucocorticoid receptor: the activated receptor binds its target sequence, modifies local chromatin structure, then leaves its site accessible to another factor.

Animals↗
PubMed1995

Interplay of glucose-stimulated Ca2+ sequestration and acetylcholine-induced Ca2+ release at the endoplasmic reticulum in rat pancreatic beta-cells.

It is known that the stimulation with high glucose initially decreases as well as subsequently increases the cytosolic free Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells. In the present study, we aimed at exploring the ionic mechanism and physiological role of the glucose-induced decrease in [Ca2+]i by measuring [Ca2+]i in single pancreatic beta-cells from normal rats. The glucose-induced decrease in [Ca2+]i in beta-cells was completely inhibited by thapsigargin (Tg), a specific inhibitor of the endoplasmic reticulum (ER) Ca2+ pump (Ca(2+)-ATPase). On the other hand, neither a Ca(2+)-free nor a low-Na+ condition significantly altered the glucose-induced decrease in [Ca2+]i. At basal glucose concentrations (1-4.5 mM), an insulin secretagogue acetylcholine (ACh) evoked a rather transient increase in [Ca2+]i in the presence and absence of extracellular Ca2+. A rise in glucose concentration from 1 to 4.5 mM produced a sustained decrease in [Ca2+]i and concomitantly augmented the ACh-evoked increase in [Ca2+]i. The resting [Ca2+]i level determined by glucose was tightly and reciprocally correlated with the peak of the [Ca2+]i response to ACh. Successive ACh pulses elicited repeated [Ca2+]i responses, which were progressively inhibited by Tg, suggesting that Ca2+ released by ACh was taken up by the ER Ca2+ pump and thus cycled. The results demonstrate that glucose decreases [Ca2+]i in pancreatic beta-cells mainly by activating the Ca2+ pump in ER from which ACh mobilizes Ca2+. Furthermore, the glucose-stimulated sequestration of Ca2+ by ER results in an augmented [Ca2+]i response to ACh, providing a mechanistic basis for the glucose-dependent action of ACh to initiate insulin secretion.

Acetylcholine↗
PubMed1994

The complex interplay of the DQB1 and DQA1 loci in the generation of the susceptible and protective phenotype for insulin-dependent diabetes mellitus.

IDDM patients of North East Italian region were molecularly typed for their HLA-DQB1 and DQA1 loci by using allele specific oligonucleotide probes and PCR amplified genomic DNA. IDDM status strongly correlated with DQB1 alleles carrying a non-aspartic acid residue in position 57 of DQ beta chain and DQA1 alleles with an arginine residue in position 52 of DQ alpha chain. Genotype analysis revealed that individuals with two DQB1 alleles having a non-aspartic residue in position 57 and two DQA1 alleles with an arginine residue in position 52 had the highest relative risk of disease: they constituted 41% of IDDM patients as compared to 0% of controls. Heterozygosity either at residue 57 of DQB1 or residue 52 of DQA1 was sufficient to abrogate statistical significance for disease association, although 43.6% of IDDM patients were included in these two groups as compared to 21.6% of normal controls. On the other hand the presence of two DQB1 alleles with aspartic acid in position 57 was sufficient to confer resistance to disease irrespective of the DQA1 genotype. Based on the number of possible susceptible heterodimers an individual can form, it was found that 85% of IDDM cases could form two or more heterodimers (two in cis and two in trans), but no IDDM case was found to form one susceptible heterodimer in cis. These results demonstrate that the complete HLA-DQ genotype, more than single DQB1 or DQA1 alleles or DQB1-DQA1 haplotypes, is associated with the highest risk of disease. Screening of the population for preventive purposes and/or early signs of IDDM should then take advantage of this result and "susceptible homozygous" individuals should be followed very closely and considered the first group of choice for possible new therapeutical trials.

Alleles↗
PubMedDate not supplied

Interplay of complement and cytokines in the pathogenesis of septic shock.

Sepsis is a clinical syndrome that is usually induced by bacterial infections. It is generally assumed that the syndrome results from an excessive triggering of endogenous inflammatory mediators by the invading microorganisms. These mediators include substances released by activated monocytes, macrophages, endothelial cells and neutrophils such as cytokines, reactive oxygen species and proteases, as well as activation products of coagulation, fibrinolysis, contact and complement systems. Recent studies have suggested that cytokines and complement activation products may have overlapping biological activities. In addition, multiple interactions in vitro as well as in vivo between cytokines and complement have been described. Here we will review some of these recent studies and will discuss their relevance for the pathogenesis of sepsis and septic shock.

Animals↗