Inhibition Of Total Protein Synthesis Research Articles

Cytotoxic effects of puromycin on the Golgi apparatus of pancreatic acinar cells, hepatocytes and ameloblasts.

A single injection of puromycin was given to rats in a dose sufficient to produce almost total inhibition of protein synthesis in pancreas and liver. By 10 min after injection, Golgi saccules in pancreatic acinar cells, hepatocytes and ameloblasts appeared grossly and irregularly distended, and almost devoid of content. In pancreas the condensing vacuoles near the inner face of the Golgi were often altered, and those normally present in ameloblasts were lacking. Between 2 and 3 hr after injection, protein synthesis had started anew. At this time, granules without limiting membranes appeared within cisternae of the rough endoplasmic reticulum in acinar cells and ameloblasts. These intracisternal granules are believed to consist of newly synthesized secretory protein which could not be transported through the disrupted Golgi apparatus to be packaged into secretory granules. Indeed, by 3 hr postinjection the secretory granules which normally abound in the apical processes of ameloblasts were sparce or absent. Thus, while biochemical evidence indicates that puromycin blocks protein synthesis on the ribosomes, the use of this antibiotic in vivo results in alterations in the Golgi apparatus and interruption of the packaging of protein into secretory granules.

Streptomycin action: greater inhibition of Escherichia coli ribosome function with exogenous than with endogenous messenger ribonucleic acid.

Inhibition of protein synthesis by streptomycin was tested in extracts from a strain of Escherichia coli sensitive to streptomycin. Three kinds of messenger ribonucleic acid (RNA) were employed: endogenous cellular RNA, extracted cellular RNA, and phage R17 RNA. Protein synthesis directed by extracted cellular RNA was inhibited three- to fourfold more than protein synthesis directed by endogenous RNA. With R17 RNA as messenger, nearly total inhibition of protein synthesis at initiation was again observed. The greater inhibition of function of extracted RNA, which must initiate new polypeptide chains in vitro, is in accord with the observation that in whole cells streptomycin blocks ribosomes at an early stage in protein synthesis. When streptomycin was added at successively later times during protein synthesis, the subsequent inhibition was progressively less. This was observed with either extracted cellular RNA or phage R17 RNA. A model is presented that can explain the less drastic inhibition by streptomycin of messenger RNA that is already functioning on ribosomes.

Stoffwechselregulation durch den Zellwandbaustein Kieselsäure: Polgrößenänderungen von a-Ketoglutarsäure, Aminosäuren und Nucleosidphosphaten

When the centric diatom Cyclotella cryptica is grown in a Si (OH) 4-free medium, the glutamic acid pool decreases within 3 hours to a third of the original value, whereas the aspartic acid pool is reduced by only about 20 per cent. The pools of nucleosid-triphosphates and of glycerol-1-phosphate remain unaffected during this time. The nucleosid-diphosphates pool decreases in the same way as that of aspartic acid. The decrease in the glutamic acid pool precedes the inhibition of total protein synthesis in Si (OH) 4-deficient cells, and a significant decrease in the a-ketoglutarate pool precedes the decrease of the glutamic acid content. Already within 60 minutes ofter incubation in a Si (OH) 4-free medium, the content of a-ketoglutarate is decreased to one third of the normal value. On the other hand, the acetyl CoA pathway (enhanced fatty acid synthesis) is not inhibited. The results suggest, that the Si (OH) 4-metabolism interferes with reactions between the condensing enzyme (acetyl-CoA and oxalacetate) and a-ketoglutarate. The delay between inhibition of protein- and RNA-synthesis and the different changes in the pools of amino acids and nucleosid-triphosphates resemble the regulation of the nucleosid-triphosphate pool and RNA-synthesis in amino acid starved strains of E. coli (EDLIN and NEUHARD) 1, though the primary causes are quite different.

Action of phyenethyl alcohol on the synthesis of macromolecules in Escherichia coli.

Prevost, C. (University of California, Berkeley), and V. Moses. Action of phenethyl alcohol on the synthesis of macromolecules in Escherichia coli. J. Bacteriol. 91:1446-1452. 1966.-A kinetic study of the effects of various concentrations of phenethyl alcohol on the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), protein, and beta-galactosidase in Escherichia coli has confirmed that RNA synthesis, rather than DNA synthesis, is first and most affected by phenethyl alcohol. The presence of inducer did not protect beta-galactosidase synthesis from inhibition by phenethyl alcohol. Little preferential inhibition of beta-galactosidase synthesis was observed; this is in contrast to the severe catabolite repression which results from partial inhibition of total protein synthesis caused by chloramphenicol or starvation for a required amino acid. We found no evidence that messenger RNA synthesis was inhibited to a greater extent than total RNA synthesis.