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At least 19 recordsLinked to original sources
PubMed2005

Rate of gene transfer from mitochondria to nucleus: effects of cytoplasmic inheritance system and intensity of intracellular competition.

Endosymbiotic theory states that mitochondria originated as bacterial intracellular symbionts, the size of the mitochondrial genome gradually reducing over a long period owing to, among other things, gene transfer from the mitochondria to the nucleus. Such gene transfer was observed in more genes in animals than in plants, implying a higher transfer rate of animals. The evolution of gene transfer may have been affected by an intensity of intracellular competition among organelle strains and the organelle inheritance system of the organism concerned. This article reveals a relationship between those factors and the gene transfer rate from organelle to nuclear genomes, using a mathematical model. Mutant mitochondria that lose a certain gene by deletion are considered to replicate more rapidly than normal ones, resulting in an advantage in intracellular competition. If the competition is intense, heteroplasmic individuals possessing both types of mitochondria change to homoplasmic individuals including mutant mitochondria only, with high probability. According to the mathematical model, it was revealed that the rate of gene transfer from mitochondria to the nucleus can be affected by three factors, the intensity of intracellular competition, the probability of paternal organelle transmission, and the effective population size. The gene transfer rate tends to increase with decreasing intracellular competition, increasing paternal organelle transmission, and decreasing effective population size. Intense intracellular competition tends to suppress gene transfer because it is likely to exclude mutant mitochondria that lose the essential gene due to the production of lethal individuals.

Cell Nucleus↗
PubMed1989

Intracellular competition for component chains determines class II MHC cell surface phenotype.

Mixed isotype (E alpha A beta and A alpha E beta) dimers are not found on Ia+ hematopoietic cells, although some pairs (e.g., E alpha A beta d) reach the membrane of transfected cells expressing only the two relevant class II genes. To examine the basis for this difference in potential versus actual Ia molecule expression, we utilized an L cell transfection model more closely resembling the normal condition of multiple class II alpha and beta chain synthesis within a single cell, such that competition among alpha and beta chains could occur. The surface expression of individual Ia dimers was compared with the available class II chains in such cells. Our data indicate that 3- to 5-fold preferences in assembly or transport of the predominant A alpha A beta and E alpha E beta species preclude expression of the mixed isotype E alpha A beta pair under physiologic conditions of balanced chain synthesis, but that asymmetric chain synthesis can lead to the expression of such mixed dimers on the cell surface in biologically significant amounts.

Animals↗
PubMed1994

Drug competition for intracellular triiodothyronine-binding sites.

A variety of substances, including frusemide, non-esterified fatty acids (NEFAs) and non-steroidal anti-inflammatory drugs (NSAIDs), can compete for triiodothyronine (T3)-binding sites in serum and at the cell surface. We examined the competitive potency of these agents at intracellular T3-binding sites in order to assess their potential to act as T3 antagonists. Competition for [125I]T3 binding was determined using hydroxyapatite separation in cytosols and nuclear extracts prepared from livers of Macaca fascicularis. The T3 affinities were 15.8 +/- 1.2 nmol/l in cytosol and 0.23 +/- 0.02 nmol/l in nuclear extract. Dose-response curves were analysed by a four-parameter sigmoid curve-fitting program to determine competitor potency. The nineteen agents tested included various NSAIDs, NEFAs, non-bile acid cholephils (NBACs), frusemide, amiodarone and the flavonoid EMD 21388. In nuclear extract the most active competitors were linoleic acid (8.5 mumol/l) and linolenic acid (7.8 mumol/l). Potencies of NSAIDs varied between 66 mumol/l (meclofenamic acid) and 525 mumol/l (diclofenac). In cytosol, NEFAs were less potent but NSAIDs were stronger competitors than in nuclear extract. Half-inhibitory potencies in cytosol were between 13.2 mumol/l (meclofenamic acid) and 63.1 mumol/l (flufenamic acid). The NBAC bromosulphthalein was one of the most potent inhibitors in both cytosol and nuclear extract. When expressed relative to T3, diclofenac was a more effective competitor in cytosol than it was in nuclear extract. Amiodarone and EMD 21388 were without effect both in cytosol and nuclear extract. Frusemide (759 mumol/l) was weakly active in cytosol only.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1980

Evolutionary consequences of intracellular organelle competition.

The review discusses some consequences of the widespread partial uncoupling of the reproduction of organelle DNA from that of nuclear DNA. I propose that in certain circumstances natural selection favors intraorganismal reproductive competition between different varieties of organelle DNA, and in other circumstances selection favors competition between organelle and nuclear DNA. Evidence is marshalled to show that such competition occurs in nature. Situations which would lead to selection for both kinds of competition are described and are shown to be relatively common. A number of examples of apparent competition of predicted kinds are presented. Several testable predictions are made from the theory, and it is shown that the available data are in accord with them. Similar kinds of reproductive competition are predicted to occur in some other symbiotic relationships, and possible examples are presented for two of them: bacterial plasmids and endozoic algae.

Animals↗
PubMed1983

Studies on the bioavailability of zinc in humans: mechanism of the intestinal interaction of nonheme iron and zinc.

The mechanisms of the previously described competitive zinc:iron interaction were explored in healthy human volunteers, using the increment in plasma zinc concentration after an oral dose of 25 mg of zinc as zinc sulfate as the index of zinc absorption. Ferric iron in a 2:1 Fe/Zn ratio reduced the plasma uptake of zinc, but to a significantly lesser degree than ferrous iron; addition of 1 g of ascorbic acid increased the magnitude of the inhibitory effect of ferric iron to that seen with ferrous iron. An inverse relationship between some indices of iron status in adult women, or of parenteral iron administration in a child, and the magnitude of zinc:iron interaction was observed. Saturation of the intestinal mucosa with consecutive-day doses of therapeutic iron did not influence the uptake of zinc administered alone or in the context of a 2:1 ferrous iron:zinc ratio in solution. The results are most consistent with a combination of an intraluminal competition of the two minerals and an intracellular competition at a site "distal" to the regulatory step by which iron nutriture modulates the entry of iron into the body, but "proximal" to the site at which the daily administration of therapeutic doses of iron blocked the passage of dietary iron.

Adult↗
PubMed2006

Micro-chemical imaging of cesium distribution in Arabidopsis thaliana plant and its interaction with potassium and essential trace elements.

Cesium as an alkali element exhibits a chemical reactivity similar to that of potassium, an essential element for plants. It has been suggested that Cs phytotoxicity might be due either to its competition with potassium to enter the plant, resulting in K starvation, or to its intracellular competition with K binding sites in cells. Such elemental interactions can be evidenced by chemical imaging, which determines the elemental distributions. In this study, the model plant Arabidopsis thaliana was exposed to 1 mM cesium in the presence (20 mM) or not of potassium. The quantitative imaging of Cs and endogenous elements (P, S, Cl, K, Ca, Mn, Fe, and Zn) was carried out using ion beam micro-chemical imaging with 5 microm spatial resolution. Chemical imaging was also evidenced by microfocused synchrotron-based X-ray fluorescence (microXRF) which presents a better lateral resolution (<1 microm) but is not quantitative. Cesium distribution was similar to potassium which suggests that Cs can compete with K binding sites in cells. Cesium and potassium were mainly concentrated in the vascular system of stems and leaves. Cs was also found in lower concentration in leaves mesophyll/epidermis. This late representing the larger proportion in mass, mesophyll/epidermis can be considered as the major storage site for cesium in A. thaliana. Trichomes were not found to accumulate cesium. Interestingly, increased Mn, Fe, and Zn concentrations were observed in leaves at high chlorosis. Mn and Fe increased more in the mesophyll than in veins, whereas zinc increased more in veins than in the mesophyll suggesting a tissue specific interaction of Cs with these trace elements homeostasis. This study illustrates the sensitivity of ion beam microprobe and microfocused synchrotron-based X-ray fluorescence to investigate concentrations and distributions of major and trace elements in plants. It also shows the suitability of these analytical imaging techniques to complement biochemical investigations of metallic stress in plants.

Arabidopsis↗
PubMed1999

Induction of intracellular arginase activity does not diminish the capacity of macrophages to produce nitric oxide in vitro.

The hypothesis was tested that induction of arginase expression in macrophages (M phi) diminishes nitric oxide (NO) synthesis due to intracellular competition between arginase and inducible nitric oxide synthase (iNOS) for L-arginine (L-arg). Murine M phi cell lines and bone marrow-derived M phi (BMM) were stimulated to express either iNOS or arginase or to co-express these two enzymes. The response pattern obtained was complex but allowed the following conclusions: (i) iNOS and arginase are differentially regulated. (ii) High intracellular arginase levels do not limit the capacity of M phi to synthesize NO even when the L-arg concentration in the culture medium is lowered to physiological levels. (iii) Arginase levels in BMM pre-exposed to either M phi colony-stimulating factor (M-CSF) or granulocyte-M phi colony-stimulating factor (GM-CSF) differ markedly, but iNOS expression and NO synthesis by the two BMM types is similar. (iv) Regulation of iNOS and arginase differs between primary murine bone marrow M phi and murine M phi cell lines. (v) Arginase activity appears to be inhibited during high-output NO synthesis. Taken together, our results show that NO production by M phi is not compromised by conditions that increase intracellular arginase activity.

Animals↗
PubMed2005

A segmented form of foot-and-mouth disease virus interferes with standard virus: a link between interference and competitive fitness.

Serial passage of foot-and-mouth disease virus (FMDV) in BHK-21 cells at high multiplicity of infection resulted in dominance of particles containing defective RNAs that were infectious by complementation in the absence of standard viral RNA. In the present study, we show that the defective FMDV particles interfere with replication of the cognate standard virus. Coinfections of defective FMDV with standard FMDV mutants that differ up to 151-fold in relative fitness have documented that the degree of interference is higher for low fitness than for high fitness standard virus. These comparisons suggest a likely overlap between those mechanisms of intracellular competition that underlie viral interference and those expressed as fitness differences between two viruses when they coinfect the same cells. Interference may contribute to the selective pressures that help maintain dominance of segmented defective RNAs over the standard FMDV genome.

Animals↗
PubMed1998

Six unrelated HLA-DR-matched adults recognize identical CD4+ T cell epitopes from influenza A haemagglutinin that are not simply peptides with high HLA-DR binding affinities.

Influenza A/Beijing/32/92 (H3N2) haemagglutinin (HA)-specific short-term CD4+ T cell lines were generated from six unrelated HLA-DR0701, 1501 positive adults (aged 27-60 years) 3 months following administration of an influenza subunit vaccine containing HA A/Beijing/32/92. Epitope recognition was examined using 118 HA A/Beijing/32/92-specific 16mer peptides which overlapped by 11 residues and which spanned the entire molecule. Following influenza vaccination the donors recognized identical HA peptides. The selected peptides represented HA regions which have been free from extensive drift mutation since the emergence of human H3N2 influenza A strains. Using DAP DR7.0701 cells (a murine cell line expressing HLA-DR0701) as antigen-presenting cells the majority of CD4+ T cell responses were shown to be HLA-DR0701 restricted. The relationship between HA peptide recognition and relative strength of HA peptide-HLA-DR0701 binding was then explored in a competition assay with biotinylated CLIP peptide. Although peptides representing dominant HA epitopes bound to DR0701, the relationship between relative strength of binding and immunodominance was complex, and many strongly binding peptides, particularly those with glycosylation sites and showing inter-strain variation, were not recognized. These results illustrate the control HLA class II exerts over CD4+ T cell HA epitope selection in unrelated adult humans. Immunodominance appears not to be directly related to the relative strength of HA peptide-HLA class II binding, and thus reflects complex interactions between antigen processing, intracellular competition for HLA binding, TCR repertoires and repeated exposure to different strains of influenza A viruses.

Adult↗
PubMed2003

Synthesis, comparative photosensitizing efficacy, human serum albumin (site II) binding ability, and intracellular localization characteristics of novel benzobacteriochlorins derived from vic-dihydroxybacteriochlorins.

In a sequence of reactions, methyl mesopyropheophorbide a, mesochlorin e(6) trimethyl ester, mesochlorin p(6) trimethyl ester, mesopurpurin-18-N-hexylimide methyl ester, and mesopurpurin-18-N-3,5-bis(trifluoromethyl)benzylimide methyl ester were synthesized from chlorophyll-a. These chlorins on reacting with osmium tetraoxide produced the corresponding vic-dihydroxybacteriochlorins. The 8-vinylchlorins obtained by refluxing the related vic-dihydroxybacteriochlorins in o-dichlorobenzene were individually treated with dimethylacetylenedicarboxylate (DMAD) under Diels-Alder reaction conditions. The intermediate adducts on 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) treatment rearranged to the corresponding stable benzobacteriochlorins, exhibiting the longest wavelength absorption in the range of 737 to 805 nm. In preliminary in vitro (RIF tumor cells) and in vivo screening (C3H/HeJ mice bearing RIF tumors), some of these compounds were found to be quite effective. Under similar treatment conditions (drug dose: 5.0 micromol/kg; light dose: 135 J/cm(2), tumors were exposed to light for 30 min at 24 h postinjection), the benzobacteriochlorins containing N-substituted-imide ring system produced enhanced photosensitizing efficacy with limited skin phototoxicity. These compounds were also found to bind to site II of human serum albumin (HSA). However, no correlation between the binding constant values and photosensitizing efficacy was observed. A competitive intracellular localization study of these novel structures with Rhodamine-123 (a mitochondrial probe) indicated their preferential localization in mitochondria, without producing any specific displacement of (3)H-PK11195 (PBR probe, (3)H-labeled 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide). These results suggest that the mitochondrial peripheral benzodiazepine receptor (PBR) is not the cellular binding site for this class of compounds.

Animals↗
PubMed2001

The widespread effect of beta 1,4-galactosyltransferase on N-glycan processing.

We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta 1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP-N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N-acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d-mannoside beta 1,6-N-acetylglucosaminyltransferase). The beta 1,4-GalT-I gene was introduced into Chinese hamster ovary (CHO) cells producing human interferon (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta 1,4-GalT were isolated. As we previously reported, parental IM4/V/IV cells express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily tetraantennary sugar chains. The branching of sugar chains on hIFN-gamma was suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the intracellular activity of beta 1,4-GalT relative to GnTs. Moreover, the contents of hybrid-type and high-mannose-type sugar chains increased in these clones. The results showed that beta 1,4-GalT widely affects N-glycan processing by competing with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other mechanisms that suppress the conversion of high-mannose-type sugar chains to the hybrid type.

Animals↗
PubMed1991

Extinction of the HPV18 upstream regulatory region in cervical carcinoma cells after fusion with non-tumorigenic human keratinocytes under non-selective conditions.

'Universal fuser' clones of a human papillomavirus type 16 positive cervical carcinoma cell line (SiHa) were established to study the effect of a non-tumorigenic fusion partner on the regulation of a stably integrated chloramphenicol acetyltransferase (CAT) gene controlled by the HPV18 upstream regulatory region under non-selective conditions. The CAT expressing cells were fused with both non-tumorigenic, spontaneously immortalized human keratinocytes (HaCaT) and non-modified SiHa cells. The resulting hybrids were characterized by restriction enzyme fragment length polymorphism analysis and flow cytometry. While the non-selectable, HPV18-driven indicator gene is constitutively expressed in SiHa cells, the CAT activity is extinguished in SiHa x HaCaT cells, but still present in SiHa x SiHa hybrids. Examination of the cytokeratin expression pattern reveals that the keratinocyte phenotype seems not only to be dominant in terms of the extinction of the HPV18 regulatory region but also by the conservation of most of the differentiation markers of the non-tumorigenic fusion partner. Cycloheximide treatment and intracellular competition experiments using the transient COS7 fusion-amplification technique are accompanied by the reactivation of the marker gene in previously CAT- SiHa x HaCaT hybrids. These data strongly suggest that trans-acting negative regulatory factors derived from the non-malignant human keratinocytes are responsible for the extinction phenomenon.

Animals↗
PubMed1982

Effects of Na readmission on cellular 45Ca fluxes in Na-depleted guinea pig taenia coli.

The removal of Na from the medium causes a cellular Ca uptake in the smooth muscle of the guinea pig taenia coli which is rapidly reversed if medium Na is readmitted. This net extrusion was characterized in tissues which were first Na-depleted in a zero-Na (sucrose) solution. Li was able to substitute for Na in mediating this effect. K was also able to mimic Na in this respect if the depolarization-mediated Ca influx caused by the isotonic K solution was blocked with 10(-5) M D -600. The net Ca extrusion upon Na readmission was due to a small decrease in Ca influx, as well as a marked increase in the transmembrane Ca efflux rate, as revealed by 45Ca washout experiments. The increased 45Ca efflux upon Na readmission could be mimicked by Li, K, choline and tris. We conclude that the Na/Ca-exchange hypothesis is insufficient to explain these data, in that both Ca extrusion and 45Ca efflux can be stimulated in the absence of a Na gradient, or in the absence of any monovalent cationic gradient. These observations are discussed in terms of a possible intracellular competition of Ca and monovalent cations for anionic binding sites, as well as with regard to a possible direct stimulation of a plasmalemmal CaATPase by monovalent cations.

Animals↗
PubMed1999

Xenotransplantation: the importance of the Galalpha1,3Gal epitope in hyperacute vascular rejection.

The transplantation of organs from other species into humans is considered to be a potential solution to the shortage of human donor organs. Organ transplantation from pig to human, however, results in hyperacute rejection, initiated by the binding of human natural antidonor antibody and complement. The major target antigen of this natural antibody is the terminal disaccharide Galalphal,3Gal, which is synthesized by Galbeta1,4GlcNAc alpha1,3-galactosyltransferase. Here we review our current knowledge of this key enzyme. A better understanding of structure, enzyme properties, and expression pattern of alpha1,3-galactosyltransferase has opened up several novel therapeutic approaches to prevent hyperacute vascular rejection. Cloning, and expression in vitro of the corresponding cDNA, has allowed to develop strategies to induce immune tolerance, and deplete or neutralize the natural xenoreactive antibody. Elucidation of the genomic structure has led to the production of transgenic animals that are lacking alpha1,3-galactosyltransferase activity. A detailed knowledge of the enzyme properties has formed the basis of approaches to modify donor organ glycosylation by intracellular competition. Study of the expression pattern of alpha1,3-galactosyltransferase has helped to understand the mechanism of hyperacute rejection in discordant xenotransplantation, and that of complement-mediated, natural immunity against interspecies transmission of retroviruses.

Animals↗
PubMed1992

Binding of tissue plasminogen activator to human endothelial cells. Importance of the B-chain as a ligand.

The aim of the present study was to investigate the binding of tissue plasminogen activator (tPA) to cultured endothelial cells and to characterize binding structures present in the cultures. Studies on the binding of 125I-tPA to cultured endothelial cells from human umbilical-cord veins (HUVEC) indicated that the number of sites for specific binding of tPA is 8 x 10(5) per cell. Treatment with an excess of antibodies against plasminogen-activator inhibitor type 1 (PAI-1) caused an 80% decrease in the binding, leaving about 1.6 x 10(5) unoccupied binding sites per cell, which appeared to be different from PAI-1. About 1.9 x 10(5) binding sites/cell for tPA were found on the surface of HUVEC that had been detached from the matrix. This indicates that only minor amounts of PAI-1 occur on the surface of the cells. In addition, immunocytochemical analysis showed that PAI-1 antigen is present almost exclusively in the cytoplasm but was not observed on the surface of the cells, whereas tPA antigen is abundant on the plasma membrane of tPA-treated cells as well as intracellularly. Competition studies using unlabelled compounds showed that native tPA and tPA B-chain (the proteinase domain), as well as the inactive derivatives, B-chain inactivated with D-Phe-Pro-Arg-chloromethane and tPA-PAI-1 complex, caused a considerable quenching of the binding of 125I-tPA to HUVEC, whereas the isolated A-chain had no demonstrable effect. Two components (apparent molecular masses 38 kDa and 56 kDa) reacting with tPA but lacking PAI-1 antigen determinants were identified. Thus the data suggest that tPA binds to HUVEC by two principally different mechanisms. One is mediated by PAI-1, which binds and inactivates tPA with a functional active site. The other binding is achieved by components which react with sites on the activator molecule other than structures of the A-chain or the active site.

Cell Membrane↗
PubMed1986

Regulation of rat insulin 1 gene expression: evidence for negative regulation in nonpancreatic cells.

Two cis-acting elements, the enhancer and the promoter, independently contribute to the cell-specific expression of the rat insulin 1 gene. The activities of these elements are presumably mediated by trans-acting factors. We have performed intracellular competition experiments that suggest the presence of a negative factor(s) that represses the enhancer activity in cells that do not express the insulin gene. In these experiments fibroblast cells (COS-7) were transfected with two plasmids: a test plasmid containing the gene for chloramphenicol acetyltransferase under the control of the thymidine kinase promoter and the insulin enhancer; and a competitor plasmid containing insulin enhancer sequences and the simian virus 40 origin of replication to permit its replication in the recipient cells. The presence of the competitor plasmid led to a 5- to 6-fold increase in chloramphenicol acetyltransferase activity as compared with the activity detected when insulin enhancer was absent from either the competitor or the test plasmid. A 5-fold increase in chloramphenicol acetyltransferase activity was also seen when the rat amylase enhancer was present on the competitor plasmid; in contrast the simian virus 40 enhancer exerted no effect. Efficient derepression required additional sequences downstream from those essential for enhancer activity. We propose that the activity of the rat insulin 1 enhancer is modulated by a negative trans-acting factor(s) that is active in cells not expressing insulin but is overridden by the dominant positive trans-acting factor(s) present in insulin-producing cells.

Animals↗