Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis

Science ◽  
2002 ◽  
Vol 295 (5552) ◽  
pp. 140-143 ◽  
Author(s):  
Y. Maeshima
Keyword(s):  
Protein Synthesis ◽  
Endothelial Cell ◽  
Specific Inhibitor ◽  
Inhibitor Of Protein Synthesis

Enhancement of tumor necrosis factor-induced endothelial cell injury by cycloheximide

1990 ◽  
Vol 259 (2) ◽  
pp. L123-L129
Author(s):  
K. B. Nolop ◽  
U. S. Ryan
Keyword(s):  
Endothelial Cells ◽  
Protein Synthesis ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Morphological Evidence ◽  
Human Aorta ◽  
Dependent Manner ◽  
Inhibitor Of Protein Synthesis ◽  
Necrosis Factor

Tumor necrosis factor (TNF), a potent polypeptide mediator released by activated monocytes and macrophages, has a number of proinflammatory effects on endothelial cells. TNF is cytotoxic to tumor cells in vivo and in vitro, but TNF-induced toxicity to endothelial cells is less well established. We now report that cycloheximide (CHX), an inhibitor of protein synthesis, renders endothelial cells highly susceptible to TNF-induced lysis. TNF alone did not change the overall rate of protein synthesis by endothelial cells, whereas the addition of CHX completely abolished protein synthesis. Endothelial cells incubated in TNF alone in high concentrations (up to 1,000 U/ml) showed minimal rounding up and release of 51Cr. Likewise, CHX alone (5 micrograms/ml) had no significant effect on endothelial cell morphology and release of 51Cr. However, incubation of endothelial cells in both CHX and TNF caused injury in a dose-dependent manner. Morphological evidence of cell retraction, rounding, and detachment began within 2 h, but specific 51Cr release did not begin to rise until after 4 h. These changes were not observed when endothelial cells were incubated with TNF/CHX at 4 degrees C. The combination of TNF/CHX was lethal to all endothelial cells tested (bovine pulmonary artery, human umbilical vein, and human aorta), with human aortic cells showing the most pronounced changes. We conclude that healthy endothelial cells are resistant to TNF-induced lysis, but inhibition of their ability to make protein renders them highly susceptible.

scholarly journals THE EFFECT OF ACTIDIONE ON MITOSIS IN THE SLIME MOLD PHYSARUM POLYCEPHALUM

1965 ◽  
Vol 27 (2) ◽  
pp. 337-341 ◽  
Author(s):  
J. E. Cummins ◽  
E. N. Brewer ◽  
H. P. Rusch
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Nucleic Acid ◽  
Physarum Polycephalum ◽  
Specific Inhibitor ◽  
Slime Mold ◽  
Amino Acid Incorporation ◽  
Late Prophase ◽  
Acid Incorporation ◽  
Inhibitor Of Protein Synthesis

Actidione, reportedly a specific inhibitor of protein synthesis, was found to reduce the incorporation of labeled amino acids into proteins of the slime mold Physarum polycephalum without drastically inhibiting the incorporation of nucleic acid precursors into RNA. This inhibitor was found to completely block the ensuing mitosis if it was added at any time between telophase and late prophase. Plasmodia given Actidione in late prophase (about the time of nucleolar dissolution) went on through telophase to reconstruction even though nuclear amino acid incorporation was drastically reduced during that period.

scholarly journals STUDIES ON THE MECHANISM OF ACTION OF PEDERINE

1968 ◽  
Vol 36 (3) ◽  
pp. 485-496 ◽  
Author(s):  
Agnese Brega ◽  
Arturo Falaschi ◽  
Luigi De Carli ◽  
Mario Pavan
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Cytotoxic Effect ◽  
Rna Synthesis ◽  
Cultured Cells ◽  
Specific Inhibitor ◽  
Cytological Examination ◽  
Effect Analysis ◽  
Inhibitor Of Protein Synthesis

Pederine, a drug extracted from the coleopter Paederus fuscipes, inhibits the growth of in vitro cultured cell lines at concentrations of the order of 1.5 nanogram/ml. Cytological examination shows a generalized cytotoxic effect. Analysis of macromolecular syntheses by the use of radioactive precursors shows that pederine causes an almost immediate block of protein and DNA synthesis, without affecting RNA synthesis. The effects on the synthesis of the two types of macromolecules remain nearly simultaneous even at the lowest active concentrations of pederine. Studies with cell-free systems show that the drug inhibits protein synthesis, whereas it is ineffective on the DNA-polymerizing activity. It seems, therefore, that the drug acts primarily on the amino acid-polymerizing system, and that the effect on DNA is secondary. This idea is strengthened by the observation that puromycin, a specific inhibitor of protein synthesis, also affects promptly DNA synthesis of in vitro cultured cells. Other authors have shown the same phenomenon with a number of inhibitors of protein synthesis; the properties of pederine support, therefore, the view that continuous protein synthesis is necessary for the maintenance of DNA replication in higher organisms.

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