Determinants of kinin release in isolated rat hindquarters

1998 ◽  
Vol 274 (1) ◽  
pp. R120-R125 ◽  
Author(s):  
Tohru Sakakibara ◽  
Thomas H. Hintze ◽  
Alberto Nasjletti
Keyword(s):  
Protein Synthesis ◽  
Trypsin Inhibitor ◽  
De Novo ◽  
Soybean Trypsin Inhibitor ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Bicarbonate Buffer ◽  
Kallikrein Inhibitor ◽  
Isolated Rat

We studied the determinants of kinin release into the venous effluent of rat hindquarters perfused with Krebs bicarbonate buffer. Kinin release in preparations perfused with control media (14.6 ± 2.5–20.7 ± 6.7 pg/15 min) was surpassed by that in preparations perfused with media containing kininase inhibitors (243 ± 53 to 276 ± 78 pg/15 min). Kinin release increased when purified kininogen (from 242 ± 43 to 3,365 ± 725 pg/15 min) or kallikrein (from 270 ± 49 to 30,649 ± 8,040 pg/15 min) was added to the perfusate. Conversely, kinin release fell when the kallikrein inhibitor aprotinin (from 272 ± 58 to 122 ± 27 pg/15 min) or soybean trypsin inhibitor (from 273 ± 52 to 195 ± 25 pg/15 min) was added. Both basal and kininogen-induced kinin release were attenuated in preparations perfused with media containing cycloheximide, a protein synthesis inhibitor, but kallikrein-induced kinin release was not. These data suggest that kinin release from perfused rat hindquarters reflects the activity of both the kinin-degrading and kinin-generating pathways and that the latter is sustained by a kallikrein manufactured de novo and by preexistent kininogen(s).

scholarly journals Social Fear Memory Requires Two Stages of Protein Synthesis in Mice

2020 ◽  
Vol 21 (15) ◽  
pp. 5537
Author(s):  
Johannes Kornhuber ◽  
Iulia Zoicas
Keyword(s):  
Protein Synthesis ◽  
Temporal Dynamics ◽  
De Novo ◽  
Fear Memory ◽  
Protein Synthesis Inhibitor ◽  
Dependent Manner ◽  
Synthesis Inhibitor ◽  
Systemic Injection ◽  
Social Fear ◽  
Two Stages

It is well known that long-term consolidation of newly acquired information, including information related to social fear, require de novo protein synthesis. However, the temporal dynamics of protein synthesis during the consolidation of social fear memories is unclear. To address this question, mice received a single systemic injection with the protein synthesis inhibitor, anisomycin, at different time-points before or after social fear conditioning (SFC), and memory was assessed 24 h later. We showed that anisomycin impaired the consolidation of social fear memories in a time-point-dependent manner. Mice that received anisomycin 20 min before, immediately after, 6 h, or 8 h after SFC showed reduced expression of social fear, indicating impaired social fear memory, whereas anisomycin caused no effects when administered 4 h after SFC. These results suggest that consolidation of social fear memories requires two stages of protein synthesis: (1) an initial stage starting during or immediately after SFC, and (2) a second stage starting around 6 h after SFC and lasting for at least 5 h.

scholarly journals Signal transduction for chemotaxis and haptotaxis by matrix molecules in tumor cells.

1990 ◽  
Vol 110 (4) ◽  
pp. 1427-1438 ◽  
Author(s):  
S Aznavoorian ◽  
M L Stracke ◽  
H Krutzsch ◽  
E Schiffmann ◽  
L A Liotta
Keyword(s):  
Protein Synthesis ◽  
Matrix Protein ◽  
Type Iv Collagen ◽  
De Novo ◽  
Protein Synthesis Inhibitor ◽  
Dependent Manner ◽  
Recognition Sequence ◽  
Synthesis Inhibitor ◽  
Concentration Dependent Manner ◽  
Type Iv

Transduction of signals initiating motility by extracellular matrix (ECM) molecules differed depending on the type of matrix molecule and whether the ligand was in solution or bound to a substratum. Laminin, fibronectin, and type IV collagen stimulated both chemotaxis and haptotaxis of the A2058 human melanoma cell line. Peak chemotactic responses were reached at 50-200 nM for laminin, 50-100 nM for fibronectin, and 200-370 nM for type IV collagen. Checkerboard analysis of each attractant in solution demonstrated a predominantly directional (chemotactic) response, with a minor chemokinetic component. The cells also migrated in a concentration-dependent manner to insoluble step gradients of substratum-bound attractant (haptotaxis). The haptotactic responses reached maximal levels at coating concentrations of 20 nM for laminin and type IV collagen, and from 30 to 45 nM for fibronectin. Pretreatment of cells with the protein synthesis inhibitor, cycloheximide (5 micrograms/ml), resulted in a 5-30% inhibition of both chemotactic and haptotactic responses to each matrix protein, indicating that de novo protein synthesis was not required for a significant motility response. Pretreatment of cells with 50-500 micrograms/ml of synthetic peptides containing the fibronectin cell-recognition sequence GRGDS resulted in a concentration-dependent inhibition of fibronectin-mediated chemotaxis and haptotaxis (70-80% inhibition compared to control motility); negative control peptide GRGES had only a minimal effect. Neither GRGDS nor GRGES significantly inhibited motility to laminin or type IV collagen. Therefore, these results support a role for the RGD-directed integrin receptor in both types of motility response to fibronectin. After pretreatment with pertussis toxin (PT), chemotactic responses to laminin, fibronectin, and type IV collagen were distinctly different. Chemotaxis to laminin was intermediate in sensitivity; chemotaxis to fibronectin was completely insensitive; and chemotaxis to type IV collagen was profoundly inhibited by PT. In marked contrast to the inhibition of chemotaxis, the hepatotactic responses to all three ligands were unaffected by any of the tested concentrations of PT. High concentrations of cholera toxin (CT; 10 micrograms/ml) or the cAMP analogue, 8-Br-cAMP (0.5 mM), did not significantly affect chemotactic or haptotactic motility to any of the attractant proteins, ruling out the involvement of cAMP in the biochemical pathway initiating motility in these cells. The sensitivity of chemotaxis induced by laminin and type IV collagen, but not fibronectin, to PT indicates the involvement of a PT-sensitive G protein in transduction of the signals initiating motility to soluble laminin and type IV collagen.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Effect of emetine, a protein synthesis inhibitor, on larval tail resorption in the ascidian Halocynthia roretzi

2006 ◽  
Vol 23 (2) ◽  
pp. 43-46
Author(s):  
Kiyotaka Matsumura ◽  
Manami Nagano ◽  
Sachiko Tsukamoto ◽  
Haruko Kato ◽  
Nobuhiro Fusetani
Keyword(s):  
Protein Synthesis ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Halocynthia Roretzi

scholarly journals Local protein synthesis of neuronal MT1-MMP for agrin-induced presynaptic development

Development ◽  
2021 ◽  
Vol 148 (10) ◽  
Author(s):  
Jun Yu ◽  
Marilyn Janice Oentaryo ◽  
Chi Wai Lee
Keyword(s):  
Protein Synthesis ◽  
Neuronal Development ◽  
Neuromuscular Junctions ◽  
Neuronal Cell ◽  
Time Lapse ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Local Protein Synthesis ◽  
Presynaptic Differentiation ◽  
Local Protein

ABSTRACT Upon the stimulation of extracellular cues, a significant number of proteins are synthesized distally along the axon. Although local protein synthesis is crucial for various stages throughout neuronal development, its involvement in presynaptic differentiation at developing neuromuscular junctions remains unknown. By using axon severing and microfluidic chamber assays, we first showed that treatment of a protein synthesis inhibitor, cycloheximide, inhibits agrin-induced presynaptic differentiation in cultured Xenopus spinal neurons. Newly synthesized proteins are prominently detected, as revealed by the staining of click-reactive cell-permeable puromycin analog O-propargyl-puromycin, at agrin bead-neurite contacts involving the mTOR/4E-BP1 pathway. Next, live-cell time-lapse imaging demonstrated the local capturing and immobilization of ribonucleoprotein granules upon agrin bead stimulation. Given that our recent study reported the roles of membrane-type 1 matrix metalloproteinase (MT1-MMP) in agrin-induced presynaptic differentiation, here we further showed that MT1-MMP mRNA is spatially enriched and locally translated at sites induced by agrin beads. Taken together, this study reveals an essential role for axonal MT1-MMP translation, on top of the well-recognized long-range transport of MT1-MMP proteins synthesized from neuronal cell bodies, in mediating agrin-induced presynaptic differentiation.

Protein synthesis requirement of the Aplysia circadian clock. Tested by active and inactive derivatives of the inhibitor anisomycin

1980 ◽  
Vol 85 (1) ◽  
pp. 33-42
Author(s):  
J. W. Jacklet
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Compound Action Potential ◽  
Phase Shifts ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Inhibitor Molecule ◽  
Group 5 ◽  
Characteristic Effect ◽  
Derivatives Of

1.The circadian rhythm of compound action potential frequency recorded from the isolated eye of Aplysia in culture medium and darkness was subjected to 6 h pulse treatments with either anisomycin, a protein synthesis inhibitor, or inactive derivatives of anisomycin. 2. Anisomycin caused phase-dependent phase shifts of the rhythm as expected from previous experiments, but none of the derivative molecules caused phase shifts or perturbed the rhythm. 3. Anisomycin inhibited eye-protein synthesis by 75% at the concentrations (10(−6) M) used in the phase shifting experiments but none of the derivatives inhibited synthesis. 4. Only those molecules that actually inhibited protein synthesis caused phase shifts of the clock, although the inactive derivatives differed from anisomycin by only an acetyl group. 5. The results strengthen the conclusion that the inhibition of protein synthesis caused by anisomycin is important in perturbing the timing of the circadian clock and not some other characteristic effect of the inhibitor molecule. Together with the results from other systems, these findings imply that the daily synthesis of protein is a general requirement for circadian clocks.

scholarly journals Transforming Potential of the Herpesvirus Oncoprotein MEQ: Morphological Transformation, Serum-Independent Growth, and Inhibition of Apoptosis

1998 ◽  
Vol 72 (1) ◽  
pp. 388-395 ◽  
Author(s):  
Juinn-Lin Liu ◽  
Ying Ye ◽  
Lucy F. Lee ◽  
Hsing-Jien Kung
Keyword(s):  
Protein Synthesis ◽  
Target Genes ◽  
Rapid Development ◽  
Fibroblast Cell ◽  
Protein Synthesis Inhibitor ◽  
Morphological Transformation ◽  
Synthesis Inhibitor ◽  
Necrosis Factor Alpha ◽  
Downstream Target ◽  
T Cell Lymphomas

ABSTRACT Marek’s disease virus (MDV) induces the rapid development of overwhelming T-cell lymphomas in chickens. One of its candidate oncogenes, meq (MDV Eco Q) which encodes a bZIP protein, has been biochemically characterized as a transcription factor. Interestingly, MEQ proteins are expressed not only in the nucleoplasm but also in the coiled bodies and the nucleolus. Its novel subcellular localization suggests that MEQ may be involved in other functions beyond its transcriptional potential. In this report we show that MEQ proteins are expressed ubiquitously and abundantly in MDV tumor cell lines. Overexpression of MEQ results in transformation of a rodent fibroblast cell line, Rat-2. The criteria of transformation are based on morphological transfiguration, anchorage-independent growth, and serum-independent growth. Furthermore, MEQ is able to distend the transforming capacity of MEQ-transformed Rat-2 cells through inhibition of apoptosis. Specifically, MEQ can efficiently protect Rat-2 cells from cell death induced by multiple modes including tumor necrosis factor alpha, C2-ceramide, UV irradiation, and serum deprivation. Its antiapoptotic function requires new protein synthesis, as treatment with a protein synthesis inhibitor, cycloheximide, partially reversed MEQ’s antiapoptotic effect. Coincidentally, transcriptional induction of bcl-2 and suppression of bax are also observed in MEQ-transformed Rat-2 cells. Taken together, our results suggest that MEQ antagonizes apoptosis through regulation of its downstream target genes involved in apoptotic and/or antiapoptotic pathways.

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