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Biomedical subjects

G Dirheimer

Publications and source records attributed to G Dirheimer.

At least 127 records · Page 7Linked to original sources
PubMed1983

Effects of ochratoxin A metabolites on yeast phenylalanyl-tRNA synthetase and on the growth and in vivo protein synthesis of hepatoma cells.

The ochratoxin A (OTA) metabolite (4R)-4-hydroxyochratoxin A [4R)-OTA) inhibits the aminoacylation of phenylalanine tRNA catalyzed by phenylalanyl-tRNA synthetase (PheRS) with a Ki-value of 0.9 mM as compared to 1.3 mM for OTA. It also inhibits protein synthesis and cell growth in the same manner as OTA. Ochratoxin alpha (OT alpha) does not affect either protein synthesis or cell growth.

Amino Acyl-tRNA Synthetases↗
PubMed1983

Comparative study of the effect of ochratoxin A analogues on yeast aminoacyl-tRNA synthetases and on the growth and protein synthesis of hepatoma cells.

Ochratoxin A (OTA), a naturally occurring mycotoxin of Aspergillus and Penicillium species, consists of a 5' chlorinated dihydromethyl isocoumarin linked to L,beta-phenylalanine by an alpha-amide bond. 8 analogues of OTA were prepared in which the phenylalanine was always substituted by another amino acid. The effects of these analogues on yeast tRNA amino acylation reaction and on growth and protein synthesis of hepatoma culture cells were compared with those of OTA. In addition, Ochratoxin B (OTB) and ochratoxin alpha (OT alpha) were examined. All the analogues of OTA had inhibitory effects in the 3 test systems, although to a lesser degree than OTA. The degree of inhibition depended on the kind of substituted amino acid, the tyrosine, valine, serine and alanine analogues being most effective, in contrast to the proline analogue. OTB and OT alpha were ineffective.

Amino Acyl-tRNA Synthetases↗
PubMed1983

Effects of two metabolites of ochratoxin A, (4R)-4-hydroxyochratoxin A and ochratoxin alpha, on immune response in mice.

The metabolites of ochratoxin A, (4R)-4-hydroxyochratoxin A and ochratoxin alpha, were investigated for immunosuppressive properties in BALB/c mice. The standard plaque-counting technique for the estimation of antibody-producing spleen lymphocytes was used. (4R)-4-hydroxyochratoxin A was found to be an immunosuppressor almost as highly effective as ochratoxin A. Doses of 1 microgram of (4R)-4-hydroxyochratoxin A per kg administered to mice caused an 80% reduction in the number of cells producing immunoglobulin M (90% with ochratoxin A) and a 93% reduction in cells synthesizing immunoglobulin G (92% with ochratoxin A). Ochratoxin alpha, however, was ineffective. A possible mode of action is discussed.

Animals↗
PubMed1983

[Demonstration and partial purification of a convulsant from Cnestis glabra (Connaracea): effect on cells in culture].

A dialysable and thermostable compound was partially purified from Cnestis glabra (Connaracea) seeds. It is insoluble in organic solvents. At a dose corresponding to 0.5 g of seeds it has a lethal effect on mice after convulsive attacks. Sodium dipropylacetate, an anticonvulsive agent prevents the convulsions but not the death of the animals. The toxic compound inhibits protein synthesis in a rabbit reticulocyte lysate and in hepatoma tissue culture; moreover in the cell culture, the incorporation of thymidine into DNA is inhibited.

Animals↗
PubMed1982

[Incubation of Beef tRNALeu in interferon-treated cells lysate leads to a partial removal of the 3' terminal sequence (author's transl)].

Beef tRNALeu and tRNAArg labeled with [32P]-phosphate at their 3' hydroxyl or 5'-phosphate ends have been incubated in the presence of lysates of interferon-treated Mouse cells. The degradation of the two tRNAs has been followed by polyacrylamide slab gel electrophoresis. In all cases, the incubation leads to a degradation of the tRNAs to a variable extent, but tRNALeu is degraded much faster than tRNAArg. This study, provides evidence that the 3' terminal C - C - A is the primary target of degradation leading to a very fast inactivation of tRNALeu and to the inhibition of translation of exogenous and synthetic mRNAs.

Animals↗
PubMed1982

Comparison of different methods of recovering DNA from a methylation assay.

Several enzymes, for example DNA (cytosine-5-)-methyltransferase, produce relatively strong interactions with DNA and hinder the quantitative recovery of this DNA from a reaction mixture. Classical methods like the Sevag chloroform-iso-amylic alcohol one or the phenol procedure lead only to a 50-60 per cent recovery of the DNA. A new procedure was worked out utilizing pancreatic RNase, proteinase K, NaOH 0.5 M treatment and trichloracetic acid precipitation which gives 85 per cent recovery of DNA.

DNA↗
PubMed1981

Mechanism of inhibition of enzymatic deoxyribonucleic acid methylation by 2-(acetylamino)fluorene bound to deoxyribonucleic acid.

Binding of 2-(acetylamino)fluorene (AAF) to C-8 of guanine induces a local destabilization of the DNA helix. A relationship was observed where the degree of DNA modification by AAF was inversely proportional to its methyl acceptor capacity from S-adenosyl-L-methionine in the presence of rat brain DNA cytosine 5-methyltransferase. Moreover, substituted DNA (DNA-AAF) behaves as a methylation inhibitor of native DNA. This inhibition is of the mixed type. The substituted DNAs have higher affinities for the enzyme than native DNA. The inhibition is irreversible. Addition of DNA-AAF to the enzyme preincubated with native DNA inhibits methylation, but only after a lag period. This agrees with the model in which the methylase "walks" along the strand to methylate cytosine residues before being detached from the DNA. AAF bound to guanine residues may block the movement of the enzyme along the helix. Single-stranded DNA has an affinity for the methylase 1.6 times lower than that of native double-stranded DNA. On the other hand, single-stranded DNA-AAF is more methylated than double-stranded DNA-AAF. A tentative model taking into account these observations is presented under Discussion. The in vitro hypomethylation of DNA-AAF could explain the in vivo observations made by several authors.

2-Acetylaminofluorene↗
PubMed1980

Yeast mitochondrial methionine initiator tRNA: characterization and nucleotide sequence.

Two methionine tRNAs from yeast mitochondria have been purified. The mitochondrial initiator tRNA has been identified by formylation using a mitochondrial enzyme extract. E. coli transformylase however, does not formylate the yeast mitochondrial initiator tRNA. The sequence was determined using both 32P-in vivo labeled and 32P-end labeled mt tRNAf(Met). This tRNA, unlike N. crassa mitochondrial tRNAf(Met), has two structural features typical of procaryotic initiator tRNAs: (i) it lacks a Watson-Crick base-pair at the end of the acceptor stem and (ii) has a T-psi-C-A sequence in loop IV. However, both yeast and N. crassa mitochondrial initiator tRNAs have a U11:A24 base-pair in the D-stem unlike procaryotic initiator tRNAs which have A11:U24. Interestingly, both mitochondrial initiator tRNAs, as well as bean chloroplast tRNAf(Met), have only two G:C pairs next to the anticodon loop, unlike any other initiator tRNA whatever its origin. In terms of overall sequence homology, yeast mitochondrial tRNA(Met)f differs from both procaryotic or eucaryotic initiator tRNAs, showing the highest homology with N. crassa mitochondrial initiator tRNA.

Acyltransferases↗