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At least 91 records · Page 5Linked to original sources

Ca2+ signalling in rat chromaffin cells: interplay between Ca2+ release from intracellular stores and membrane potential.

Cytosolic Ca2+ oscillations are physiologically important in a range of excitable and non-excitable cells. The combined techniques of whole-cell patch clamp and photometric measurement of cytosolic Ca2+ has enabled us to identify the components of Ca2+ spiking in rat chromaffin cells. We show that Ca2+ oscillations continue at a fixed membrane potential and that infusion of the InsP3 receptor antagonist, heparin, substantially blocked the cytosolic Ca2+ spikes. However, even in the presence of heparin we observed spikes of membrane potential depolarization due to the repetitive activation of a transient inward cation current. We conclude that Ca2+ oscillations are dependent on Ca2+ release from heparin sensitive Ca2+ stores and possibly on Ca2+ entry associated with the repetitive activation of a transient cation current. The depolarizing action of the cation current would, in turn, recruit voltage-sensitive Ca2+ channels and further Ca2+ entry would augment the cytosolic Ca2+ spikes. Our results demonstrate that Ca2+ oscillations in rat chromaffin cells are due to a complex interplay of Ca2+ entry and Ca2+ release.

Adrenal Medulla↗

The interplay between Salmonella typhimurium and its macrophage host--what can it teach us about innate immunity?

Salmonella enterica sv. Typhimurium (S. typhimurium) is a genetically tractable, facultative intracellular pathogen, whose capacity to cause systemic disease in mice depends upon its ability to survive and replicate within macrophages. The identification of Salmonella mutants that lack this activity, has provided a tool with which to dissect the mechanisms used by Salmonella to establish a permissive niche, and identify host activities which it must overcome in order to achieve this. Salmonella actively maintains itself within an intracellular vacuole, thereby shielding itself from an antibacterial activity of host macrophage cytosol. Salmonella controls the maturation of its vacuole, segregating itself from the macrophage degradative pathway. Like several other pathogens, Salmonella reduces the effectiveness of bacteriocidal and bacteriostatic free radicals generated by macrophages, by synthesising enzymes and products that counteract them. Recent evidence indicates that Salmonella also avoids free radical-dependent macrophage antimicrobial mechanisms by more novel means. Here, we review recent studies of the interplay between pathogen and host, with particular emphasis on those areas that suggest new facets to the cell biology of macrophages, and their innate immune functions.

Animals↗

CAMP and Ca2+ interplay: a matter of oscillation patterns.

Ca(2+) and cAMP signalling pathways are tightly interconnected and the cellular effects mediated by the two second messengers depend strictly on reciprocal modulation. The signalling network that derives from such interplay holds the potential for expanding the information content of the signal enormously and, thus, can contribute substantially to the specificity and diversity of the response. Recent work points to interdependent Ca(2+) and cAMP oscillation patterns as a new paradigm for signal transduction.

Animals↗

Interplay of signaling pathways in plant disease resistance.

Plants are under constant threat of infection by pathogens armed with a diverse array of effector molecules to colonize their host. Plants have, in turn, evolved sophisticated detection and response systems that decipher pathogen signals and induce appropriate defenses. Genetic analysis of plant mutants impaired in mounting a resistance response to invading pathogens has uncovered a number of distinct, but interconnecting, signaling networks that are under both positive and negative control. These pathways operate, at least partly, through the action of small signaling molecules such as salicylate, jasmonate and ethylene. The interplay of signals probably allows the plant to fine-tune defense responses in both local and systemic tissue.

Acetates↗

A GABA-neuropeptide Y (NPY) interplay in LH release.

Neuropeptide Y (NPY) stimulates and gamma-amino butyric acid (GABA) inhibits LH release in the rat. Since a sub-population of NPY-producing neurons in the arcuate nucleus (ARC) of the hypothalamus co-express GABA, the possibility of an interplay between NPY and GABA in the release of LH was investigated in two ways. First by employing light and electron microscopic double staining for NPY and GABA, using pre and post-immunolabeling on rat brain sections, we detected GABA in NPY immunoreactive axon terminals in the MPOA, one of the primary sites of action of these neurotransmitters/neuromodulators in the regulation of LH release. These morphological findings raised the possibility that inhibitory GABA co-released with NPY may act to restrain the excitatory effects of NPY on LH release. Muscimol (MUS, 0.44 or 1.76 nmol/rat), a GABA(A) receptor agonist, administered intracerebroventricularly (icv), alone failed to affect LH release, but NPY (0.47 nmol/rat icv) alone stimulated LH release in ovarian steroid-primed ovariectomized rats. On the other hand, administration of MUS blocked the NPY-induced stimulation of LH release in a dose-dependent manner. Similarly, administration of MUS abolished the excitatory effects on LH release of 1229U91, a selective NPY Y4 receptor agonist. These results support the possibility that in the event of co-release of these neurotransmitters/neuromodulators, GABA may act to restrain stimulation of LH release by NPY during the basal episodic and cyclic release of LH in vivo.

Animals↗

The interplay between heme iron and protein sulfhydryls in the reaction of dimeric Scapharca inaequivalvis hemoglobin with nitric oxide.

The homodimeric hemoglobin from the mollusk Scapharca inaequivalvis possesses a single reactive cysteine residue per monomer, Cys92, which is located in the subunit interface in the vicinity of the heme group. The interplay between the heme iron and Cys92 towards the reaction with NO has been investigated by the combined use of electrospray mass spectrometry, FTIR and UV-Visible spectroscopy. When the ferrous liganded or unliganded protein reacts with free NO in solution Cys92 is not modified, but undergoes nitrosation when the hemoglobin is exposed to the nitric oxide releaser S-nitrosocysteine. When the ferric protein reacts with free NO under anaerobic conditions the heme iron is reduced and Cys92 is nitrosated. At variance with other hemeproteins investigated to date, in Scapharca HbI the heme-iron NO driven reduction is not accompanied by the formation of a ferric iron nitrosyl intermediate in detectable amounts. The results are consistent with the hypothesis that the nitrosating agent is the NO(+) species, which is generated during the NO driven reduction of the ferric heme iron. The possible reaction mechanism is discussed in comparison with recent findings on human hemoglobin and myoglobin.

Animals↗

Interplay of causation between suppliers and consumers in evolutionary trophic dynamics.

Natural selection, conceived as the process of small causes making small effects on the level of molecular evolutionary dynamics of a population, can yield global effects on the level of evolutionary trophic dynamics of populations, including those of mass extinctions. Occurrence of mass extinctions is due to the interplay of causation between suppliers and consumers in trophic dynamics. If the case of supplier causation is available such that resource exploitation by consumers on the upper trophic level follows in time resource presentation by suppliers on the lower, instead of resource exploitation followed by resource presentation, mass extinctions could be a norm of the evolutionary trophic dynamics.

Biological Evolution↗

Interplay of pituitary adenylate cyclase-activating polypeptide with a silencer element to regulate the upstream promoter of the human gonadotropin-releasing hormone receptor gene.

Multiple transcription start sites were identified in the human gonadotropin releasing hormone receptor (hGnRHR) gene. Recently, an upstream promoter residing at -1727/-1674, in vicinity of a CAP site at -1673, was characterized. In this report, we elucidated the underlying mechanisms for the regulation of this promoter. Functionally, this promoter was constitutively suppressed by a silencer element (-1673/-1351) situated immediately downstream to it. On the other hand, pituitary adenylate cyclase-activating polypeptide (PACAP), via the cAMP pathway, was found to be the extracellular cue to control the upstream promoter. Following PACAP-27, PACAP-38 (30 nM) and forskolin (25 microM) treatment, there were significant increases in the reporter gene activities. By deletion analysis, the region residing at -1727 to -1577, containing the distal promoter and 97 bp of the silencer was subsequently found to be responsible for PACAP/cAMP induction. To localize the PACAP-dependent cis-acting element(s) within the silencer, block replacement scanning mutation was performed and a hGnRHR gene PACAP-responsive element (GPRE) was identified at -1676/-1648. The actions of PACAPs and forskolin on the GPRE were further evidenced by gel mobility shift assays. There was an increase in protein binding onto this element only after peptide treatment. As GnRH receptor number on gonadotrope cell surface is a key factor in regulating gonadotropin release, the present study provides an insight into the interplay between PACAP and GnRH receptors on pituitary gonadotropes to control human reproductive functions.

Base Sequence↗

Interplay of biomechanical and neuromuscular constraints on pattern stability and attentional demands in a bimanual coordination task in human subjects.

Recent debate has focused upon the issue of whether general principles and laws of movement coordination may be derived without reference to anatomical, mechanical and physiological mechanisms. It has been proposed that self-generated movement involves the interaction of biomechanical and neuromuscular constraints. Biomechanical constraints are usually considered of as arising from the pendular dimensions of the limb or limb segments whereas neuromuscular constraints are commonly associated with nervous and metabolic control processes. The present study aims to investigate the interplay between these two different constraints on bimanual pattern stability and attentional demands. Five subjects were asked to execute an anti-phase coordination pattern (180 degrees of relative phase), while gradually increasing the frequency of oscillation and changing the rotational inertia of the joysticks. Frequency manipulation was expected to affect the neuromuscular constraints. Inertial manipulation was expected to affect biomechanical constraints. Attentional demands, reflecting the central cost associated with the maintenance of the coordination pattern was assessed using a dual-task paradigm. The results showed that: (1) increasing the oscillation frequency altered both coordination dynamics and attentional demands associated with the maintenance of bimanual coordination patterns; (2) manipulation of rotational inertia of the joysticks also altered pattern stability (standard deviation of relative phase) and coordination dynamics (i.e. the number of phase transition and the before transition), but these alterations were not paralleled by a change in attentional demands.

Adrenergic Agonists↗

Functional interplay between gelatinases and hyperalgesia in endotoxin-induced localized inflammatory pain.

The role of ECM-degrading proteinases in normal developmental processes and in pathological conditions is extensively studied. However, few reports describe the role ECM-degrading proteinases play in modulating hyperalgesia. The goal of this study is to describe the regulation of gelatinases during endotoxin mediated local inflammation, induced by intra plantar endotoxin (ET; 1.25 microg/50 microl) injection in Balb/c mice, and to correlate that with hyperalgesia. ET injections induced hyperalgesia, as determined by hot plate and paw pressure tests, which peaked by 24 h and recovered by 48 h post-injection. Contralateral paw of ET injected mice and saline injected paws in control mice elicited no hyperalgesia. Zymography showed that ET and saline injected paws elicited increased gelatinase activity by 9 h after injection. However, only the former maintained high levels of expression of a 90 kD gelatinase up to at least 96 h post ET injection, while in the latter gelatinase expression was down regulated by 24 h. Interestingly, the 90-kD gelatinase was upregulated in the contralateral paw of the ET-injected mice beyond 48 h post injection. Saline injection in that paw, during a time when gelatinases are upregulated, induced hyperalgesia. Intraperitoneal injection of either ZnCl(2) (100 microM), thymulin (5 microg/100 microl), or morphine (2 mg/kg/100 microl) reversed the ET-induced hyperalgesia and suppressed gelatinase activity. Furthermore, intraperitoneal injection of MPI, an ECM-degrading proteinase inhibitor, reversed ET induced hyperalgesia. Taken together, the above suggests that a functional interplay exists between gelatinase upregulation triggered by ET injections and hyperalgesia. The exact mechanism underlying such correlation remains to be determined.

Animals↗

The dynamic interplay of malignant and benign T cells in cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma is a malignancy of functional, tissue-specific T cells. Many characteristics of the disease can be explained by virtue of the ability of the malignant cell population to actively participate in the host's immunologic network. Various aspects of this dynamic interplay between malignant and benign T cells are discussed, including impact on diagnosis, staging, and therapy.

Diagnosis, Differential↗

Regulation of enzymatic lipid peroxidation: the interplay of peroxidizing and peroxide reducing enzymes.

For a long time lipid peroxidation has only been considered a deleterious process leading to disruption of biomembranes and thus, to cellular dysfunction. However, when restricted to a certain cellular compartment and tightly regulated, lipid peroxidation may have beneficial effects. Early on during evolution of living organisms special lipid peroxidizing enzymes, called lipoxygenases, appeared and they have been conserved during phylogenesis of plants and animals. In fact, a diverse family of lipoxygenase isoforms has evolved starting from a putative ancient precursor. As with other enzymes, lipoxygenases are regulated on various levels of gene expression and there are endogenous antagonists controlling their cellular activity. Among the currently known mammalian lipoxygenase isoforms only 12/15-lipoxygenases are capable of directly oxygenating ester lipids even when they are bound to membranes and lipoproteins. Thus, these enzymes represent the pro-oxidative part in the cellular metabolism of complex hydroperoxy ester lipids. Its metabolic counterplayer, representing the antioxidative part, appears to be the phospholipid hydroperoxide glutathione peroxidase. This enzyme is unique among glutathione peroxidases because of its capability of reducing ester lipid hydroperoxides. Thus, 12/15-lipoxygenase and phospholipid hydroperoxide glutathione peroxidase constitute a pair of antagonizing enzymes in the metabolism of hydroperoxy ester lipids, and a balanced regulation of the two proteins appears to be of major cell physiological importance. This review is aimed at summarizing the recent developments in the enzymology and molecular biology of 12/15-lipoxygenase and phospholipid hydroperoxide glutathione peroxidase, with emphasis on cytokine-dependent regulation and their regulatory interplay.

Animals↗

Triple quantum MQMAS spectroscopy of 59Co(I = 7/2) in Na3Co(NO2)6 and trans-Co[(en2)(NO2)2]NO3 interplay between the quadrupole coupling and anisotropic shielding tensors.

The purpose of this paper is to investigate the interplay between the chemical shielding anisotropy and quadrupole interaction in MQMAS spectra. 59Co in the compounds Na3Co(NO2)6 and trans-Co[(en2)(NO2)2]NO3 provides model systems for such an investigation. Furthermore, only few results have been reported on the application of the MQMAS method to a spin I = 7/2. The possibilities of the MQMAS spectroscopy for determining the relative orientation of the two tensors and its advantage over previous techniques are discussed. Reported experimental spectra at different spinning speeds of Na3Co(NO2)6 are accurately reproduced by our theoretical simulations. The calculations are based on a recent approach, summarized in the present paper, which allows one to perform efficient simulations of MQMAS spectra including all interactions and their time-dependence throughout the experiment. This is necessary for calculating accurate MQMAS spectra including the spinning sideband pattern. In the case of trans-Co[(en2)(NO2)2]NO3 where the quadrupolar interaction and chemical shielding are stronger and their axes are non-coincident, the MQMAS spectrum is strongly distorted due to the unsufficient spinning speed and RF power. In this case, MAS at different spinning speeds is shown to provide valuable information.

Anisotropy↗

Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways.

Cadherins play important roles in cell-cell adhesion during tissue differentiation. Cadherins are linked to the actin cytoskeleton by catenins (beta-catenin/armadillo, plakoglobin, and alpha-catenin). Recent results show that beta-catenin also binds to another cytoskeletal complex containing the adenomatous polyposis coli protein and microtubules, and interacts with several signaling pathways that include tyrosine kinases and phosphatases and Wnt/Wingless. Interplay between these cytoskeletal complexes and signaling pathways may regulate morphogenesis.

Animals↗

Spermatogenesis in the vitamin A-deficient rat: possible interplay between retinoic acid receptors, androgen receptor and inhibin alpha-subunit.

In order to understand the mechanisms of retinol action on the testis, testicular retinoic acid receptor alpha, beta(RAR alpha and beta), androgen receptor (AR) and inhibin alpha-subunit were studied in normal, vitamin A-deficient (VAD) and vitamin A-supplemented rats by immunohistochemistry and immunoblotting. Compared to the normal testis, expression of 110 K AR was up-regulated by vitamin A withdrawal, whereas 51 K RAR alpha remained unchanged. An additional 55 K RAR alpha signal was observed. Readministration of retinol caused a marked decrease of AR in the VAD testis. By 24 h, AR declined to below the normal level. Although the 51 K RAR alpha signal remained unchanged, the 55 K band was slightly up-regulated at 6 h after retinol administration. A 51 K RAR beta protein was seen in the VAD but in not the normal testis. The intensity of the 51 K RAR beta band remained constant before and after the administration of retinol, but it had a slight up-shift at 6 h after retinol injection, suggesting post-translational modification of the receptor. The inhibin alpha-subunit of 18 K protein was undetectable in the VAD testis and increased to above normal level at 24 h after retinol administration. Immunohistochemically, nuclear AR immunostaining was more intense in the VAD testis than in the normal testis. The intensity of immunostaining declined in all AR-positive cells after the injection of retinol, but the decrease was more evident in Sertoli than in other cells. At 24 h after retinol the immunostaining was undetectable in most Sertoli cells. The regulation of the inhibin alpha-subunit by retinol in the cytoplasm of Sertoli cells detected by immunohistochemistry was correlated to the results in immunoblotting. These results suggest a possible interplay between retinoids, androgen and inhibin signalling systems in Sertoli cells in the regulation of spermatogenesis during retinol action.

Animals↗

Interplay of TBP inhibitors in global transcriptional control.

The TATA binding protein (TBP) is required for the expression of nearly all genes and is highly regulated both positively and negatively. Here, we use DNA microarrays to explore the genome-wide interplay of several TBP-interacting inhibitors in the yeast Saccharomyces cerevisiae. Our findings suggest the following: The NC2 inhibitor turns down, but not off, highly active genes. Autoinhibition of TBP through dimerization contributes to transcriptional repression, even at repressive subtelomeric regions. The TAND domain of TAF1 plays a primary inhibitory role at very few genes, but its function becomes widespread when other TBP interactions are compromised. These findings reveal that transcriptional output is limited in part by a collaboration of different combinations of TBP inhibitory mechanisms.

Binding Sites↗

Interplay of global regulators and cell physiology in the general stress response of Escherichia coli.

Under various stress conditions, two sigma subunits of RNA polymerase, sigmaS and sigma70, coexist in Escherichia coli cells. In contrast to sigma70, sigmaS is subject to intricate regulation and coordinates an emergency reaction to stress as well as long term stress adaptation. In vivo, the two sigma factors clearly control different genes. Yet, they are structurally and functionally very similar and basically recognize the same promoter sequences. Recent data suggest that sigma factor specificity at stress-activated promoters is affected by the interplay of the two RNA polymeraseholoenzymes with additional regulatory factors, such as H-NS, Lrp, CRP, IHF or Fis, that differentially affect transcription initiation by sigmaS or sigma70 in a promoter-specific manner.

Adaptation, Biological↗

Interplay in lipoplexes between type of pDNA promoter and lipid composition determines transfection efficiency of human growth hormone in NIH3T3 cells in culture.

This study was aimed to investigate if and to what extent there is an interplay between lipoplex physicochemical properties and plasmid promoter type affecting transfection efficiency in vitro. To reduce the number of variables only one cell type (NIH3T3 cells), one gene (human growth hormone), one cationic lipid (DOTAP) in a plasmid >85% in supercoiled form, and the same medium conditions were used. The variables of the physicochemical properties included presence and type of helper lipid (DOPE, DOPC, or cholesterol, all in 1:1 mole ratio with DOTAP), size and lamellarity of the liposomes used for lipoplex preparation (large unilamellar vesicles, LUV, versus multilamellar vesicles, MLV), and DNA(-)/cationic lipid(+) charge ratio, all containing the same human growth hormone but differing in their promoter enhancer region. Two of the promoters were of viral origin: (a) SV40 promoter (simian virus early promoter) and (b) CMV promoter (cytomegalovirus early promoter); two were of mammalian cell origin: (c) PABP promoter (human poly(A)-binding protein promoter) and (d) S16 promoter (mouse ribosomal protein (rp) S16 promoter). Transfection studies showed that, irrespective of promoter type, large (> or =500 nm) MLV were superior to approximately 100 nm LUV; the extent of superiority was dependent on liposome lipid composition (larger for 100% DOTAP and DOTAP/DOPE than for DOTAP/DOPC and DOTAP/cholesterol). The optimal DNA(-)/DOTAP(+) charge ratio for all types of lipoplexes used was 0.2 or 0.5 (namely, when the lipoplexes were positively charged). Scoring the six best lipoplex formulations (out of 128 studied) revealed the following order: pCMV (DOTAP/DOPE) >> pSV (DOTAP/DOPE)=pCMV(DOTAP/cholesterol)=pS16 (100% DOTAP)=pS16 DOTAP/DOPE >> pCMV (DOTAP/DOPC). The lack of trivial consistency in the transfection efficiency score, the pattern of transfection efficiency, and statistical analysis of the data suggest that there is cross-talk between promoter type and lipoplex lipid composition, which may be related to the way the promoter is associated with the lipids.

3T3 Cells↗