scholarly journals Saporin, a Polynucleotide–Adenosine Nucleosidase, May Be an Efficacious Therapeutic Agent for SARS-CoV-2 Infection

2020 ◽  
pp. 247255522097091
Author(s):  
Idris Arslan ◽  
Hafize Akgul ◽  
Murat Kara
Keyword(s):  
Ribosomal Rna ◽  
Protein Synthesis Inhibitor ◽  
Type I ◽  
Ribosome Inactivating Protein ◽  
Synthesis Inhibitor ◽  
Novel Drugs ◽  
Ribotoxic Stress Response ◽  
Cell Signal Transduction ◽  
Adenosine Nucleosidase ◽  
High Enzymatic Activity

Saporin, a type I ribosome-inactivating protein from soapwort plant, is a potent protein synthesis inhibitor. Catalytically, saporin is a characteristic N-glycosidase, and it depurinates a specific adenine residue from a universally conserved loop of the major ribosomal RNA (rRNA) of eukaryotic cells. It is well-known that saporin induces apoptosis through different pathways, including ribotoxic stress response, cell signal transduction, genomic DNA fragmentation and RNA abasic lyase (RAlyase) activity, and NAD+ depletion by poly-(ADP)-ribose polymerase hyperactivation. Saporin’s high enzymatic activity, high stability, and resistance to conjugation procedures make it a well-suited tool for immunotherapy approaches. In the present study, we focus on saporin-based targeted toxins that may be efficacious therapeutic agents for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our discussed points suggest that saporin may be a strategic molecule for therapeutic knockout treatments and a powerful candidate for novel drugs in the struggle against coronavirus 2019 (COVID-19).

Modulation of Arachidonic Acid Metabolism in Human Endothelial Cells by Glucocorticoids

1986 ◽  
Vol 55 (03) ◽  
pp. 369-374 ◽  
Author(s):  
Raffaele De Caterina ◽  
Babette B Weksler
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Arachidonic Acid Metabolism ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Prolonged Incubation ◽  
Dependent Inhibition ◽  
Human Thrombin ◽  
Umbilical Vein Endothelial Cells

SummaryTo learn whether glucocorticoids inhibit prostaglandin (PG) production in vascular endothelial cells, we investigated the effects of glucocorticoids on PG synthesis by cultured human umbilical vein endothelial cells (EC). Pretreatment of EC with dexamethasone (DX, 10-9 to 5 x 10-5 M) caused a dose-dependent inhibition of PGI2 production when PG synthesis from endogenous arachidonate was stimulated by human thrombin (0.25-2 U/ml) or ionophore A 23187 (1-5 μM). The inhibition was detectable at 10-7 M DX and maximal at 10-5 M (4.0 ± 0.7 vs. control: 7.7 ± 1.9 ng/ml, mean ± S.D., P <0.01). The production of PGE2 and the release of radiolabelled arachidonate (AA) from prelabelled cells were similarly inhibited. Prolonged incubation of EC with glucocorticoids was required to inhibit PG production or arachidonate release: ranging from 8% inhibition at 5 h to 44% at 38 h. In contrast, prostaglandin formation from exogenous AA was not altered by DX treatment. When thrombin or ionophore-stimulated EC were restimulated with exogenous AA (25 μM), DX-treated cells released more PGI2 than control cells (5.7 ± 0.5 vs. 4.1 ± 0.6 ng/ml, P <0.01). Both the decrease in PGI2 production after thrombin/ionophore and the increase after re-stimulation with AA were blunted in the presence of the protein synthesis inhibitor cycloheximide (0.1-0.2 μg/ml). Thus, incubation of EC with glucocorticoids inhibits PG production at the step of phospholipase activation. The time requirement for these steroid effects and their blunting by cycloheximide are consistent with the induction of regulatory proteins, possibly lipocortins, in endothelial cells.

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

Rapid qualitative changes in mRNA populations in cultured human lymphocytes: comparison of the effects of cycloheximide and concanavalin A

1984 ◽  
Vol 62 (9) ◽  
pp. 859-864 ◽  
Author(s):  
Donald R. Forsdyke
Keyword(s):  
Concanavalin A ◽  
Human Lymphocytes ◽  
Polyacrylamide Gel Electrophoresis ◽  
Lymphocyte Activation ◽  
Relative Mass ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Mrna Species ◽  
Reticulocyte Lysate ◽  
Qualitative Changes

To examine the hypothesis that the stimulation of cultured lymphocytes by lectins involves the inactivation of a protein repressor of putative "activation genes," the effects of a protein synthesis inhibitor (cycloheximide) and a lectin (concanavalin A) were compared. Qualitative changes in mRNA populations were assessed by translating RNA prepared from cycloheximide- or lectin-treated cultures in a rabbit reticulocyte lysate. [35S]Methionine-labelled translation products were analysed by two-dimensional polyacrylamide gel electrophoresis. Cycloheximide increased the radioactive labelling of cultured lymphocytes with the RNA precursor [3H]uridine, as previously reported. This was observed during the first 3 h of culture; thereafter, cycloheximide was inhibitory. The period of increased labelling with [3H]uridine coincided with a period of great increase in mRNA corresponding to an acidic protein of a relative mass of approximately 55 000. This mRNA was not detected in RNA prepared from control cultures, but was one of the most abundant mRNA species detected in RNA prepared from cycloheximide-treated cultures. Increases in certain less abundant mRNA species were also noted. However, the mRNAs were not observed in RNA prepared from lectin-treated cultures. If an increase in these mRNAs is important for lymphocyte activation, then the increase must be to an extent not detected by our current methods.

Desensitization and resensitization of lutropin receptors expressed in transfected Y-1 adrenal cells

1999 ◽  
Vol 163 (2) ◽  
pp. 289-297 ◽  
Author(s):  
GA Ulaner ◽  
J Chuang ◽  
W Lin ◽  
D Woodbury ◽  
RV Myers ◽  
...  
Keyword(s):  
Receptor Occupancy ◽  
Untranslated Regions ◽  
Protein Synthesis Inhibitor ◽  
Receptor Recycling ◽  
Synthesis Inhibitor ◽  
Early Step ◽  
Hormonal Stimulation ◽  
Adrenal Cells ◽  
Metallothionein Promoter ◽  
Stimulation Of

Stimulation of gonadal cells by lutropins such as human chorionic gonadotropin (hCG) is often transient and followed by down-regulation and/or desensitization of lutropin receptors (LHR). Here we describe desensitization/resensitization of LHR in Y-1 adrenal cell lines (termed Y-1L) expressing a rat cDNA lacking most 5' and 3' LHR untranslated regions under the control of a metallothionein promoter. Using a simple morphological assay in which stimulated cells are round and unstimulated cells are flat, we identified clones that rounded and remained round and others that became insensitive to lutropin stimulation and reverted to their flat appearance within 2-4 h. Flattened cells were insensitive to further hormonal stimulation but rounded after treatments with cholera toxin, forskolin, or cyclic AMP, showing that loss of responsiveness was associated with an early step in signal transduction, not loss of rounding potential. Removing the lutropin stimulus for at least 90-120 min reversed hormone insensitivity, even in the presence of the protein synthesis inhibitor puromycin. The number of surface bound receptors did not change during a cycle of rounding/flattening and hCG bound to rounded or flattened cells was replaced equally by radioiodinated hCG during incubations at 4 degrees C. Thus, desensitization/resensitization of LHR in Y-1L cells occurred in the absence of new receptor synthesis, receptor degradation, or receptor recycling. These observations suggest that LHR desensitization/resensitization in Y-1L cells was closely coupled to receptor occupancy and that this cell line may be useful for identifying factors that modulate the activities of occupied receptors.

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.

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