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At least 127 records · Page 7Linked to original sources
PubMed2002

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed2003

Membrane fusion: a structural perspective on the interplay of lipids and proteins.

The fusion of biological membranes is governed by the carefully orchestrated interplay of membrane proteins and lipids. Recently determined structures of fusion proteins, individual domains of fusion proteins and their complexes with regulatory proteins and membrane lipids have yielded much suggestive insight into how viral and intracellular membrane fusion might proceed. These structures may be combined with new knowledge on the fusion of pure lipid bilayer membranes in an attempt to begin to piece together the complex puzzle of how biological membrane fusion machines operate on membranes.

Lipids↗
PubMed1997

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↗
PubMed2002

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↗
PubMed2003

Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity.

The ETS domain transcription factor Elk-1 is a direct target of the MAP kinase pathways. Phosphorylation of the Elk-1 transcriptional activation domain by MAP kinases triggers its activation. However, Elk-1 also contains two domains with repressive activities. One of these, the R motif, appears to function by suppressing the activity of the activation domain. Here, we demonstrate that SUMO modification of the R motif is required for this repressive activity. A dynamic interplay exists between the activating ERK MAP kinase pathway and the repressive SUMO pathway. ERK pathway activation leads to both phosphorylation of Elk-1 and loss of SUMO conjugation and, hence, to the loss of the repressive activity of the R motif. Thus, the reciprocal regulation of the activation and repressive activities are coupled by MAP kinase modification of Elk-1.

Animals↗
PubMed1999

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↗
PubMed2001

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↗
PubMed1983

Reverse transcriptase and its associated ribonuclease H: interplay of two enzyme activities controls the yield of single-stranded complementary deoxyribonucleic acid.

The synthesis of single-stranded globin cDNA by the RNA-directed DNA polymerase activity of reverse transcriptase in the presence of oligothymidylate primers was investigated in order to determine the limitations to higher yields. The results indicated that the associated ribonuclease H activity, an integral part of reverse transcriptase, plays a large role in the synthesis of the first strand of cDNA and that the interplay of the two enzyme activities for any specific set of conditions determines the yield of single-stranded products. In both the presence and the absence of polymerization, the associated ribonuclease H catalyzed the deadenylation of mRNA, producing molecules that were somewhat shorter, highly homogeneous in size, and fully translatable into globin protein. They were also entirely lacking in the ability to serve as templates for cDNA synthesis. The reaction was completely dependent on oligothymidylate and completely independent of deoxyribonucleoside triphosphates. The initial rate of deadenylation was one-fourth the initial rate of initiation of polymerization when saturating levels of deoxyribonucleoside triphosphates were used in the polymerase reaction. In the presence of ribonuclease H activity, the DNA polymerase catalyzed the synthesis of an array of cDNAs including some that were full length. The initiation of polymerization was rate limiting: once synthesis had begun, it required 1-1.5 min to transcribe globin mRNA. However, most primers that were elongated were aborted prematurely. Maximum synthesis of full-length cDNA required stoichiometric levels of enzyme and high triphosphate levels, but regardless of conditions, the sum of completed cDNA and deadenylated mRNA accounted for only 50% of the input mRNA. The data fit a model in which synthesis of full-length cDNA molecules depends on the arrangement of primers and transcription initiation complexes on the poly(A) "tail" of mRNA.

Animals↗
PubMed2001

Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands.

Analysis of estrogen receptor alpha and beta interplay with other transcription factors is critical to the understanding of how small molecules, the cognate ligands for these receptors, selectively regulate the mode and amplitude of gene transcription by affecting receptor activity. To better understand the molecular mechanisms of selective action of estrogen receptor ligands, we characterized estrogen receptor alpha and beta (ER) interaction with the p160 family of coactivators. We also investigated how these interactions are affected by binding of specific ligands. We show that ER alpha and beta utilize different LXXLL motifs for their interaction with p160 family members. We found that significant differences exist between the affinity of the nuclear receptor interacting domain (NRID) and interaction of separate LXXLL motifs with ERs. This result indicates that a single LXXLL motif is unlikely to be sufficient for interaction with receptors, and that regions other than LXXLL motifs also participate in ER-p160 complex formation. We found that ER alpha and beta have strong affinity preferences for particular coactivators. These results suggest that ER-mediated transcription is not driven by a random mixture of ER-coactivator complexes. We also show that some ER ligands are functionally specific. We describe a ligand that binds to both receptors, but enhances only ER beta interaction with SRC1 and SRC3 while exhibiting little effect on the ER alpha interaction with these proteins. Finally, we provide data that suggest how genistein may selectively recruit coactivators when liganded to ERs. It enhances the interaction of ERs with SRC1 and SRC3, but demonstrates a minimal effect on receptor interaction with DRIP205 and CBP.

Acetyltransferases↗
PubMed1998

Interplay between S1 and S4 subsites in Kex2 protease: Kex2 exhibits dual specificity for the P4 side chain.

The yeast Kex2 protease is the prototype of a family of eukaryotic proprotein processing proteases that includes PC1, PC2, and furin. The catalytic domains of these enzymes are homologous to the degradative serine proteases of the subtilisin family. Kex2 exhibits optimal activity toward substrates with Lys or Arg at P2 and Arg at P1 (Lys-Arg or Arg-Arg cleavage sites). However, mammalian proprotein processing proteases such as furin exhibit more stringent requirements for basic residues at P4 than at P2. Here we demonstrate that Kex2 protease also recognizes P4, with dual specificity for aliphatic and basic residues. Recognition of P4 is even more readily apparent in substrates having a poor P1 residue (Lys). Kinetic analysis of a series of otherwise identical fluorogenic substrates with Lys at P1 and different residues at P4 indicates that large, aliphatic P4 residues increase kcat/KM by 100-fold. However, smaller residues or acidic residues at P4 do not. P4 Arg also confers efficient cleavage on such a substrate, but the uncharged isostere of Arg, citrulline, does not. Kex2 may thus possess distinct subsites that recognize aliphatic or basic P4 side chains. Although a favorable P4 residue can partially compensate for the defects in kcat and kcat/KM seen with Lys in place of Arg at P1, this substitution resulted in a change in rate-determining step for all substrates examined. As previously seen in the case of subtilisin, effects of substitutions at the P1 and P4 positions were not independent, suggesting that interplay between these two positions is a common feature of substrate specificity for both processing proteases and degradative enzymes of the subtilisin superfamily.

Amino Acid Sequence↗
PubMed2000

Interplay between folding/unfolding and helix/coil transitions in giant DNA.

It has been well established that double-stranded DNA undergoes a melting, or helix/coil, transition into a single-stranded coil state with an increase in temperature. On the other hand, it has recently been found that, at a fixed temperature, long DNA, larger than several kilobase pairs, exhibits a discrete transition, or switching, between elongated and folded states, preserving its double-stranded structure, with the addition of various condensation agents, such as alcohol, hydrophilic polymer, multivalent cation, and cationic surfactant. In the present study, we examined the interplay between the folding/unfolding transition and the helix/coil transition in individual giant DNA molecules, by observing the conformation of single molecular chains with fluorescence microscopy. The results indicate that the helix-to-coil transition tightly cooperates with the unfolding transition in DNA.

Circular Dichroism↗
PubMed2004

BPA-PC on a Ni111 surface: the interplay between adsorption energy and conformational entropy for different chain-end modifications.

We extend a previous dual scale modeling approach for the behavior of polymers near a metal surface to a variety of end groups. Our approach combines a coarse-grained polymer model with ab initio DFT calculations. Such a procedure was applied to a melt of phenolic-like terminated Bisphenol A-polycarbonate (BPA-PC) interacting with a (111) nickel surface (Delle Site, L.; Abrams, C. F.; Alavi, A.; Kremer, K. Phys. Rev. Lett. 2002, 89, 156103. Abrams, C. F.; Delle Site, L.; Kremer, K. Phys. Rev. E 2003, 67, 021807). This work extends this study to different chain-end modifications of BPA-PC, p-tert-butylphenolic, p-tetramethylpropylphenolic, and p-cumylphenolic. We show how the interplay between adsorption energies and conformational entropy selects different morphologies for the various melts at the interface. Implications of these results for realistic technical materials are finally discussed.

Journal Article↗
PubMed2000

Two-dimensional molecular layers: interplay of H-bonding and van der waals interactions in the self-assembly of N,N'-dialkylsulfamides

N,N'-Dialkylsulfamide molecules assemble into solid-state structures consisting of 2D layers. The 2D layers are based on a hydrogen-bonded network of the sulfamide groups and the close-packing of alkyl groups on both sides of the 2D H-bonded network. The thickness of a 2D layer is proportional to the size of the alkyl substituents. The interplay of H-bonding and van der Waals interactions leads to stable 2D layers that pack into 3D structures.

Journal Article↗
PubMed1999

Interplay between CYP3A-mediated metabolism and polarized efflux of terfenadine and its metabolites in intestinal epithelial Caco-2 (TC7) cell monolayers.

PURPOSE: To further characterize cytochrome P450 (CYP) and P-glycoprotein (Pgp) expression in monolayers of the Caco-2 cell clone TC7, a cell culture model of the human intestinal epithelium. To study the interplay between CYP3A and Pgp as barriers to intestinal drug absorption in TC7 cells using terfenadine and its metabolites as substrates. METHODS: mRNA expression of eight CYPs and Pgp was investigated in TC7 and parental Caco-2 (Caco-2p) cell monolayers using RT-PCR. The CYP3A kinetics was determined in microsomes from both cell lines. The transport, metabolism and efflux of terfenadine and its metabolites were investigated in TC7 monolayers. RESULTS: Both TC7 and Caco-2p cells expressed mRNA for Pgp and several important CYPs. However, mRNA for CYP3A4 was detectable anly from TC7 cells. The relative affinity of CYP3A for terfenadine metabolism in the two cell lines was comparable, but the maximum reaction rate in the TC7 cells was 8-fold higher. The rate of transport of terfenadine and its metabolites hydroxy-terfenadine (HO-T) and azacyclonol across TC7 monolayers was 7.1-, 3.5- and 2.1-fold higher, respectively, in the basolateral to apical direction than it was in the apical to basolateral (AP-BL) direction. Inhibition studies indicated that the efflux was mediated by Pgp. Ketoconazole increased the AP-BL transport terfenadine dramatically by inhibiting both terfenadine metabolism and Pgp efflux. CONCLUSIONS: Cell culture models such as TC7 provide qualitative information on drug interactions involving intestinal CYP3A and Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Interplay between superoxide and nitric oxide in aging and diseases.

Free radicals, superoxide and nitric oxide, are important signaling molecules, which mediate numerous physiological functions (phagocytosis, vasorelaxation, etc.). However, regulation errors may lead to free-radical-mediated damaging processes in cells and tissues. In this work, the effects of an interplay between superoxide and NO, which may be responsible for the development of aging and diseases, are considered. We are suggesting that the superoxide-mediated proton leak leading to the inhibition of oxidative phosphorylation and the competition between NO and O2*- in their reactions with cytochrome oxidase can be a cause of mitochondrial aging.

Aging↗
PubMed2001

Fission of biological membranes: interplay between dynamin and lipids.

Membrane budding and fission are the key stages of ubiquitous processes of formation of intracellular transport vesicles. We present a theoretical consideration of one of the most important types of fission machinery, which is mediated by GTPase dynamin and controlled by lipid composition of the membrane. We suggest a mechanism for collapse of a membrane neck driven by interplay between the dynamin collar and the bending elastic energy of the neck membrane. The collar plays a role of a rigid external skeleton, which imposes mechanical constraints on the neck. We show that in certain conditions the membrane of the neck loses its stability and collapses. Collapse can result from: (i) shifting of the spontaneous curvature of the neck membrane towards negative values, (ii) stretching of the dynamin collar, (iii) tightening of the dynamin collar. The three factors can act separately or concertedly. The suggested model accounts for the major experimental knowledge on membrane fission mediated by dynamin. It includes the elements of all previous models of dynamin action based on different sets of experimental results [Sever et al., Traffic 2000; 1: 385-392]. It reconciles, at least partially, the apparent contradictions between the existing alternative views on biomembrane fission machinery.

Cell Membrane↗