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T Johansen

Publications and source records attributed to T Johansen.

At least 73 records · Page 4Linked to original sources
PubMed1992

Mutagenicity of crude senna and senna glycosides in Salmonella typhimurium.

The mutagenicity of senna glycosides and extracts of senna folium and senna fructus was investigated in the Salmonella typhimurium reversion assay. Senna glycosides were inactive in all strains, except for a slight, but significant increase in mutant frequency in TA102 in the absence and presence of liver microsomes. Extracts of senna fructus and senna folium demonstrated weak activity in TA97a, TA100 and TA102 in the presence of liver microsomes, and in TA97a and TA102 in the absence of liver microsomes. A strong increase in mutant frequency (3- to 5-fold above background frequency) was observed with all extracts in TA98 in the presence of liver microsomes. This activity increased further following enzymatic hydrolysis with hesperidinase of extracts of senna fructus from one source, and could be correlated to the release of the flavonol aglycones kaempferol and quercetin. The weak or lacking activity of anthraquinone aglycones in the tested strains of Salmonella typhimurium indicates that mutagenicity can not be attributed solely to the anthraquinone content of these plant materials. The chemical nature of other mutagenic components has not been elucidated.

Animals↗
PubMed1992

Phospholipase C-mediated hydrolysis of phosphatidylcholine is a target of transforming growth factor beta 1 inhibitory signals.

Cell growth and tumor transformation can be restrained in certain cell systems by the action of transforming growth factor beta (TGF-beta). It has been established that the mechanism whereby TGF-beta 1 inhibits cell growth does not interfere with the triggering of early mitogenic signal transduction mechanisms. Phospholipase C-catalyzed hydrolysis of phosphatidylcholine (PC) is a relatively late step in the cascade activated by growth factors. Therefore, conceivably activation of phospholipase C-catalyzed hydrolysis of PC could be the target of TGF-beta 1 action. In the study reported here, we demonstrate that TGF-beta 1 inhibits the coupling of ras p21 to the activation of PC hydrolysis, which appears to be critical for the antiproliferative effects of TGF-beta 1.

Animals↗
PubMed1992

Hydrolysis of phosphatidylcholine is stimulated by Ras proteins during mitogenic signal transduction.

We have used a dominant inhibitory ras mutant (Ha-ras Asn-17) to investigate the relationship of Ras proteins to hydrolysis of phosphatidylcholine (PC) in the transduction of mitogenic signals. Expression of Ha-Ras Asn-17 inhibited NIH 3T3 cell proliferation induced by polypeptide growth factors or phorbol esters. In contrast, the mitogenic activity of PC-specific phospholipase C (PC-PLC) was not inhibited by Ha-Ras Asn-17 expression. Similarly, cotransfection with a cloned PC-PLC gene bypassed the block to NIH 3T3 cell proliferation resulting from expression of the inhibitory ras mutant. Hydrolysis of PC can therefore induce cell proliferation in the absence of normal Ras activity, suggesting that PC-derived second messengers may act downstream of Ras in mitogenic signal transduction. This was substantiated by the finding that Ha-Ras Asn-17 expression inhibited growth factor-stimulated hydrolysis of PC. Taken together, these results indicate that PC hydrolysis is a target of Ras during the transduction of growth factor-initiated mitogenic signals.

3T3 Cells↗
PubMed1992

Expression of four zebrafish wnt-related genes during embryogenesis.

The wnt gene family codes for a group of cysteine-rich, secreted proteins, which are differentially expressed in the developing embryo and are possibly involved in cellular communication. Here, we describe the polymerase chain reaction based cloning and embryonic expression patterns of four zebrafish wnt-related sequences; wnt[a], wnt[b], wnt[c] and wnt[d]. One of these genes, wnt[a], is a potential homologue of murine Wnt-3, while the other three genes most likely represent new members of the vertebrate wnt gene family. In zebrafish embryos, transcripts of wnt[a] are confined to the dorsal diencephalon, the dorsal midbrain, the rhombic lips and the dorsal portions of the spinal cord. wnt[b] is expressed in the tail bud and at considerably lower levels in the mesoderm of the head. wnt[c] transcripts are present within the diencephalon and the posterior midbrain whereas wnt[d] shows a surprisingly similar expression pattern to zebrafish wnt-1. By analogy to wnt-1, it is likely that the members of the zebrafish wnt gene family play an important role in cell-to-cell signalling during pattern formation in the neural tube and the tail bud.

Amino Acid Sequence↗
PubMed1991

Expression pattern of zebrafish pax genes suggests a role in early brain regionalization.

In vertebrates the developing hindbrain is organized in segmental units. These units provide the primary grid for differentiation and axonal outgrowth. In the more anterior regions of the brain, however, the subdivisions remain more controversial. Cellular and molecular studies of the embryonic brain in lower vertebrates such as the zebrafish, Brachydanio rerio, may reveal remnants of such subdivisions. We have isolated complementary DNA clones for two zebrafish pax genes related to Drosophila and mouse paired-box-containing segmentation genes. The expression of these two genes is confined to specific regions in the embryonic forebrain and midbrain. Strikingly, the borders of expression of the two pax genes coincide with morphological landmarks corresponding to the primary axon tracts that are generated in the embryonic brain a few hours after the initiation of expression of these genes.

Amino Acid Sequence↗
PubMed1991

Increased responsiveness of rat mast cells to compound 48/80 due to removal of extracellular magnesium. Effects of ouabain and EGTA.

A decreased secretory response of mast cells to compound 48/80 (12% of control value) after preincubation of the cells with magnesium but without calcium was partially restored by removal of magnesium. EGTA (10 microM) blocked the restoration and decreased the restored secretory activity again, while this was further increased by ouabain (1 mM). Furthermore, ouabain completely restored the decreased secretion (50% of control value) due to preincubation without the divalent cations. This may indicate that magnesium influences a pool of cellular calcium that is involved in the stimulus-secretion coupling and is available to EGTA, and ouabain did not counteract the inhibitory mechanism of magnesium.

Animals↗
PubMed1991

Requirement of phospholipase C-catalyzed hydrolysis of phosphatidylcholine for maturation of Xenopus laevis oocytes in response to insulin and ras p21.

Recent studies have demonstrated the activation of phospholipase C-mediated hydrolysis of phosphatidylcholine both by growth factors and by the product of ras oncogene, ras p21. Also, evidence has been presented indicating that the stimulation of this phospholipid-degradative pathway is sufficient to activate mitogenesis in fibroblasts. In Xenopus laevis oocytes, microinjection of transforming ras p21 is a potent inducer of maturation, whereas microinjection of a neutralizing anti-ras p21 antibody specifically inhibits maturation induced by insulin but not by progesterone. The results presented here demonstrated that microinjection of phosphatidylcholine-hydrolyzing phospholipase C is sufficient to induce maturation of Xenopus laevis oocytes. Furthermore, microinjection of a neutralizing anti-phosphatidylcholine-hydrolyzing phospholipase C specifically blocks the maturation program induced by ras p21/insulin but not by progesterone.

Animals↗
PubMed1991

Differential effect of extracellular calcium on the Na(+)-K+ pump activity in intact polymorphonuclear leucocytes and erythrocytes.

The effect of extracellular calcium on the Na(+)-K+ pump activity in human polymorphonuclear leucocytes and erythrocytes was studied and compared with the activity in mixed peritoneal leucocytes from rats. While there was maximal decrease in the pump activity (25-30%) of leucocytes from both rat and human by calcium 0.6 mM, a concentration of 0.1 mM caused a substantial decrease indicating a high sensitivity for extracellular calcium. In contrast, calcium had no effect on the pump activity in erythrocytes. The effect of calcium on the pump activity in leucocytes may be due to regulation of the influx of sodium across the plasma membrane, since in human leucocytes calcium had no effect on the pump activity if the cells were loaded with sodium.

Animals↗
PubMed1991

Mechanism of inhibition of adenylate cyclase by phospholipase C-catalyzed hydrolysis of phosphatidylcholine. Involvement of a pertussis toxin-sensitive G protein and protein kinase C.

The phospholipase C-mediated hydrolysis of phosphatidylcholine has been shown recently to be activated by a number of agonists. Muscarinic receptors, which trigger various signal transduction mechanisms including inhibition of adenylate cyclase through Gi, have been shown to be potent stimulants of this novel phospholipid degradative pathway. We demonstrate here, by exogenous addition of Bacillus cereus phosphatidylcholine-hydrolyzing phospholipase C, that phosphatidylcholine breakdown mimics the ability of carbachol to inhibit adenylate cyclase. This effect is sensitive to pertussis toxin and is entirely dependent on the presence of protein kinase C. This kinase is also required for the inhibition by carbachol of adenylate cyclase. These results suggest that the activation of phosphatidylcholine breakdown by phospholipase C may play an important role linking or favoring the coupling muscarinic receptors to Gi. Results presented here also show that phospholipase C-mediated hydrolysis of phosphoinositides by exogenous addition of Bacillus thuringiensis phosphoinositide-hydrolyzing phospholipase C does not affect adenylate cyclase, despite the fact that protein kinase C is translocated to an extent similar to that produced by the hydrolysis of phosphatidylcholine. According to the results shown here, both phospholipases also differ in their ability to down-regulate protein kinase C as well as to phosphorylate p80 and to transmodulate the binding of epidermal growth factor, two well established effects of protein kinase C in Swiss 3T3 fibroblasts. This emphasizes the complexity, from a functional point of view, of protein kinase C activation "in vivo."

Adenylate Cyclase Toxin↗
PubMed1991

Role of GTPase activating protein in mitogenic signalling through phosphatidylcholine-hydrolysing phospholipase C.

Recent evidence has accumulated showing that activation of PLC-catalysed hydrolysis of phosphatidylcholine (PC-PLC) is a critical step in mitogenic signal transduction both in fibroblasts and in oocytes from Xenopus laevis. The products of ras genes activate PC-PLC, bind guanine nucleotides, have intrinsic GTPase activity, and are regulated by a GTPase-activating protein (GAP). It has been suggested that, in addition to its regulatory properties, GAP may also be necessary for ras function as a downstream effector molecule. In this study, evidence is presented that strongly suggests that the functional interaction between ras p21 and GAP is sufficient and necessary for activation of maturation promoting factor (MPF) H1-kinase activity in oocytes, and that PC hydrolysis is critically involved in this mechanism. Therefore, we identify GAP as a further step required for signalling through PC-PLC, and necessary for the control of oocyte maturation in response to ras p21/insulin but not to progesterone.

Animals↗
PubMed1991

Zebrafish pax[zf-a]: a paired box-containing gene expressed in the neural tube.

Murine and human sequences homologous to the paired box of the Drosophila segmentation gene paired have been reported previously. Here we describe a zebrafish (Brachydanio rerio) paired box-containing clone, pax[zf-a], which is clearly distinct from reported vertebrate Pax genes. The putative protein encoded by pax[zf-a] contains a paired box and a paired-type homeobox separated by a glycine-rich, acidic linker and a carboxy-terminal end which is remarkably rich in serine, threonine and proline residues. By in situ hybridization to embryonic tissue sections and whole mount embryos, pax[zf-a] transcripts were found within restricted regions of the central nervous system and the eye. In contrast to the murine Pax genes recently characterized, pax[zf-a] is not expressed in the segmented mesoderm. At the 17 h stage, pax[zf-a] expression is detected in a defined area of the diencephalon which circumscribes the presumptive thalamus. This suggests an involvement of pax[zf-a] in pattern formation in the rostral brain. The pax[zf-a] gene is also expressed throughout the hindbrain and spinal cord. This hybridization signal is restricted to a longitudinal column which includes the basal plate. Later in development, at 36 h post-fertilization, pax[zf-a] transcripts are no longer restricted to a specific region of the diencephalon, but are distributed over the entire developing brain.

Amino Acid Sequence↗
PubMed1991

Rapid disappearance of one parental mitochondrial genotype after isogamous mating in the myxomycete Physarum polycephalum.

Five haploid amoebal strains of the myxomycete Physarum polycephalum, each with a distinct mitochondrial genotype, were crossed in all pairwise combinations. The mitochondrial genotype in the diploid plasmodia resulting from these isogamous matings were found to be transmitted uniparentally. This uniparental inheritance could be arranged in a dominant hierarchical order. Time-course analysis of the presence of mitochondrial genotypes in the zygotes and young developing plasmodia show that elimination of one parental mitochondrial genotype is virtually completed during the first two nuclear cycles in the zygote/differentiating plasmodium. To our knowledge this is the first report indicating an active mechanism involving the degradation of mitochondrial genomes in sexual crosses.

Crosses, Genetic↗
PubMed1991

Extracellular magnesium decreases the secretory response of rat peritoneal mast cells to compound 48/80 in vitro.

Exposure of rat peritoneal mast cells to magnesium in the absence of extracellular calcium resulted in a time- and dose-dependent decrease in the secretory response induced by compound 48/80. The decrease was prevented by a low extracellular concentration of calcium. Furthermore, the decreased secretory responsiveness was dose-dependently restored by the addition of calcium to the cells simultaneously with compound 48/80. Preincubation with magnesium also inhibited antigen-induced histamine secretion in a dose-dependent manner. This was reversed by the simultaneous addition of calcium and the secretory stimulus. A dose-dependent decrease in antigen induced histamine secretion that was reversed by calcium was also observed. Exposure of the mast cells to magnesium for 15 min resulted in a parallel decrease in histamine secretion and in the cellular content of 45Ca2+. These observations suggest that magnesium may decrease the secretory response by displacing the cellular calcium which is utilized in stimulus-secretion coupling.

Animals↗
PubMed1991

Dual effect of magnesium on compound 48/80-induced histamine secretion from rat peritoneal mast cells.

The effect of magnesium on the secretory response to compound 48/80 from rat peritoneal mast cells was studied. The decrease in secretion caused by calcium deprivation was enlarged by magnesium. Glucose partially counteracted the decrease caused by calcium deprivation but not the one caused by magnesium. The addition of calcium to the cells simultaneously with compound 48/80 completely restored the secretory response if magnesium was present. The response was only partially restored in a magnesium- and glucose-free medium, whereas it was almost completely restored if glucose was present. Magnesium had a considerable effect on the restoration of the secretory response of EGTA-treated cells, whereas the effect of glucose was minimal indicating that an effect on the energy metabolism was of minor importance. The secretory response could also be restored by an exposure of the cells to calcium prior to stimulation with compound 48/80. This was, however, only observed if magnesium was present and glucose had no effect. The influence of magnesium on the restoration of the secretory response may partly occur by an effect on the energy metabolism, partly by an effect on the stimulus-secretion coupling. We propose that insufficient supply of Mg2+ to the G-protein during activation by compound 48/80 might cause a suboptimal signal transduction.

Adenosine Triphosphate↗
PubMed1991

Expression of the zebrafish paired box gene pax[zf-b] during early neurogenesis.

The paired box-containing (pax) gene family encodes a group of putative transcription factors differentially expressed during embryonic development. In this study, we describe the cloning and expression of a zebrafish gene pax[zf-b], which most probably is a direct homologue to the mouse Pax2 gene. The putative protein encoded by pax[zf-b] contains a paired box, an octapeptide, but no homeobox. However, a region of homology to the N-terminal half of paired-type homeoboxes is detected C-terminal to the pax[zf-b] paired domain. In zebrafish embryos, pax[zf-b] transcripts are first seen during the formation of the neural keel. At 9-10 h of development, two laterally located transverse stripes of cells expressing the gene appear in the rostral 1/3 of the embryo. The two areas subsequently move towards the midline and form the posterior portion of the midbrain. In the following stages of development, at 10-12 h, transcripts are detected in the otic placode, the Wolffian duct including the nephritic primodium and in the optic stalk. At a later time point, beginning at 14-15 h, single cells along the spinal cord, presumably interneurons, start to express the gene. The characteristic expression pattern of pax[zf-b] in the neural tube suggests an involvement of this gene in the regionalization of the midbrain as well as in the specification of neuronal cell fates at early embryonic stages.

Amino Acid Sequence↗
PubMed1990

[The mast cell].

A review is presented of the most important morphological and functional characteristics of the mast cell. The cell is ovoid and contains heparin-containing granules in the cytoplasm. These stain metachromatically. In addition to heparin, the granules contain histamine and other inflammatory mediators. The cell is localized perivascularly in the loose connective tissue. The mast cell secretes histamine by exocytosis when it is stimulated immunologically by binding of a specific antigen to IgE molecules in the cell membrane. Histamine secretion may also be induced by non-immunological stimulators such as polymeric amines, neuropeptides and calcium-ionophores. Calcium plays an important role in the secretory process. Immunological secretion of histamine requires the presence of extracellular calcium whereas secretion induced by polymeric amines and neuropeptides can utilize the intracellular calcium depots. Phosphatide inositides released from phospholipides in connection with cell activation release calcium from the intracellular depots and probably play a part in histamine secretion. In addition, the protein phosphorylization reactions catalized by proteinkinase C, probably contribute in the process of secretion. Finally, secretion of histamine depends upon the ATP content of the cell.

Animals↗
PubMed1990

Regulation of the Na(+)-K+ pump activity and estimation of the reserve capacity in intact rat peritoneal mast cells.

Evidence is provided that regulation of the Na(+)-K+ pump activity in rat peritoneal mast cells occurs mainly through stimulation of the pump from inside the plasma membrane by sodium. It is demonstrated that there is a large reserve capacity for the exchange of intracellular sodium with extracellular potassium in these cells. The maximal pump activity was estimated to be 3230 pmol/10(6) cells per min and Km for extracellular potassium was 1.5 mM.

Animals↗