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M D Dabeva

Publications and source records attributed to M D Dabeva.

At least 37 records · Page 2Linked to original sources
PubMed1985

Ribosome biogenesis and nucleolar ultrastructure in neuronal and oligodendroglial rat brain cells.

The absolute amounts of precursor to ribosomal RNA (pre-rRNA) and ribosomal RNA (rRNA) in isolated rat brain neuronal and oligodendroglial nuclei were determined. The amount of the major pre-rRNA and rRNA species in neuronal nuclei was about twofold higher than in oligodendroglial nuclei. The relative rate of pre-rRNA synthesis in vivo was 2.3- to 2.7-fold higher in neuronal as compared with oligodendroglial nuclei. This corresponds to a 2.7-fold higher activity of the "template-bound" RNA polymerase I in isolated neuronal nuclei, whereas the activity of the "free" enzyme in both neuronal and glial nuclei was almost identical. The higher transcription rates of rRNA genes correlated with the markedly more prominent fibrillar component in neuronal nucleoli. The turnover times of the major pre-rRNA and rRNA species in neuronal and oligodendroglial nuclei were similar, except for 45S pre-rRNA, which turned over at an approximately 1.5-fold slower rate in neuronal nuclei. The relative rates of processing of pre-rRNA and of nucleocytoplasmic transport of rRNA in neuronal cells were approximately 2.7-fold higher than in oligodendroglial cells and corresponded to the differences in rRNA gene transcription rates. The established ribosome formation features correlated with an abundant (neurons) or exceedingly scarce (oligodendrocytes) nucleolar granular component. The turnover rate of cytoplasmic ribosomes in rat brain neurons was twofold slower than in oligodendrocytes, largely because of the about fivefold higher amount of ribosomes in the cytoplasm of neurons. We conclude that ribosome formation and turnover in neuronal and oligodendroglial cells are adapted to the protein synthetic levels in these two types of brain cells.

Animals↗
PubMed1984

Ribosomal RNA synthesis in liver of adrenalectomized rats after partial hepatectomy.

The ribosome formation in four experimental groups: normal, adrenalectomized, partially hepatectomized and adrenalectomized - partially hepatectomized rats was studied. Ribosomal RNA was labelled for different intervals and the transfer of the radioactivity from 45 S pre-rRNA through the nucleolar pre-rRNA and rRNA pools into cytoplasmic 28S and 18S rRNA was followed. The results show that there are at least two ways of positive control of rRNA synthesis, one of them being glucocorticoid-dependent. The acceleration of the pre-rRNA processing through the shortest maturation pathway in regenerating liver is reduced in the absence of the hormone. Glucocorticoids do not influence nucleo-cytoplasmic rRNA transport.

Adrenalectomy↗
PubMed1983

Post-transcriptional regulation of ribosome formation in the nucleus of regenerating rat liver.

Kinetic experiments on RNA labelling in vivo with [14C]orotate were performed with normal and 12h-regenerating rat liver. The specific radioactivities of nucleolar, nucleoplasmic and cytoplasmic rRNA species were analysed by computer according to the models of rRNA processing and nucleo-cytoplasmic migration given previously [Dudov, Dabeva, Hadjiolov & Todorov, Biochem. J. (1978) 171, 375-383]. The rates of formation and the half-lives of the individual pre-rRNA and rRNA species were determined in both normal and regenerating liver. The results show clearly that the formation of ribosomes in regenerating rat liver is post-transcriptionally activated: (a) the half-lives of all the nucleolar pre-rRNA and rRNA species are decreased by 30% on average; (b) the pre-rRNA processing is directed through the shortest maturation pathway: 45 S leads to 32 S + 18 S leads to 28 S; (c) the nucleo-cytoplasmic transfer of ribosomes is accelerated. As a consequence, the time for formation and appearance of ribosomes in the cytoplasm is shortened 1.5-fold for the large and 2-fold for the small subparticle. A new scheme for endonuclease cleavage of 45 S pre-rRNA is proposed, which explains the alterations in pre-rRNA processing in regenerating liver. Its validity for pre-rRNA processing in other eukaryotes is discussed. It is concluded that: (i) the control sites in the intranucleolar formation of 28 S and 18 S rRNA are the immediate precursor of 28 S rRNA, 32 S pre-rRNA, and the primary pre-rRNA, 45 S pre-rRNA, respectively; (ii) the limiting step in the post-transcriptional stages of ribosome biogenesis is the pre-rRNA maturation.

Animals↗
PubMed1983

Turnover of ribosomal 28S and 18S rRNA during rat liver regeneration.

The turnover of 28S and 18S rRNA was studied in the course of 12 d after partial hepatectomy, including the proliferative (1st to 5th d) and post-proliferative (6th to 12th d) phases of liver regeneration. Turnover data, as the day-to-day rates of synthesis and degradation of 28S and 18S rRNA, were obtained by employing a suitable experimental procedure for the estimation of the increase of the amount of rRNA in the regenerating liver. It was found that 28S and 18S rRNA are accumulated into the cytoplasm and degraded at identical rates both in the proliferative and post-proliferative phases. The turnover of both rRNA moieties is markedly slower during the first 3 d of liver regeneration.

Animals↗
PubMed1983

Turnover of ribosomes in regenerating rat liver.

The turnover of ribosomes was studied in regenerating liver and the rates of ribosome degradation in the proliferative (1-5 days) and post-proliferative (6-12 days) phases after partial hepatectomy compared: Ribosome turnover during the first 3 days is slower, the half-life of ribosomes being approximately 300 hr. Ribosome synthesis is markedly activated--39% synthesis rate, which corresponds to 34% accumulation rate per day. The half-life of ribosomes during the second phase is about 107 hr. The rate of synthesis falls down to 19% the net gain of ribosomes being 3% per day.

Animals↗
PubMed1983

Different rates of synthesis and turnover of ribosomal RNA in rat brain and liver.

The kinetics of in vivo labeling of cellular free UMP and nucleolar, nucleoplasmic, and cytoplasmic rRNA with [14C]orotate in rat brain and liver were investigated. Evaluation of the experimental data shows: (a) The rate of nucleolar precursors of ribosomal RNA (pre-rRNA) synthesis and the deduced rate of ribosome formation in brain is about fivefold lower than in liver and corresponds to 220-260 ribosomes/min/nucleus. (b) The lower rate of in vivo pre-rRNA synthesis is correlated with a lower activity of RNA polymerase I in isolated brain nuclei. (c) The half-lives of nucleolar rRNA in brain and liver are 210 and 60 min, respectively, thus showing a slower rate of processing of pre-rRNA in brain nucleoli. (d) The nucleo-cytoplasmic transport of ribosomes in brain is also markedly slower than in liver and reflects the lower rates of synthesis and processing of pre-rRNA. (e) Cytoplasmic ribosomes in brain and liver turn over with half-lives of about 6 and 4 days, respectively. It is concluded that the markedly lower rate of ribosome biogenesis in brain is specified mainly at the level of transcription of rRNA genes.

Animals↗
PubMed1982

Transcriptional control of ribosome production in regenerating rat liver.

Kinetic experiments of labelling in vivo with [14C]orotate of cellular free UMP and/or UTP, nucleolar, nucleoplasmic and cytoplasmic rRNA in normal and 12 h-regenerating rat liver were performed. The specific-radioactivity curves obtained were analysed by computer and the rates of synthesis of precursor rRNA (45S pre-rRNA) and cytoplasmic 28S and 18S rRNA calculated. (a) The rates of synthesis of 45S pre-rRNA in normal and regenerating rat liver are 1400 and 3700 molecules/min per nucleus respectively; (b) the average rates of formation of mature 28S and 18S rRNA are identical with the rates of synthesis of 45S pre-rRNA in both normal and regenerating rat liver. Thus the synthesis of rRNA in 12h-regenerating rat liver is activated 2.7-fold. The analysis of rRNA synthesis in isolated nucleoli also shows a 2.7-fold stimulation of transcription in regenerating liver. It is concluded that all the 45S pre-rRNA molecules synthesized are processed and transferred as 28S and 18S rRNA in the cytoplasm, i.e. degradation (wastage) of newly synthesized ribosomes in the nucleus does not occur in both normal and regenerating rat liver. Thus the enhanced production of ribosomes in regenerating rat liver is regulated only at the transcriptional level.

Animals↗
PubMed1982

Quantitative alterations in the nucleolar and nucleoplasmic ribosomal ribonucleic acids in regenerating rat liver.

A quantitative analysis of the nuclear pre-rRNA (precursor to rRNA) and rRNA in normal and 12h-regenerating rat liver was carried out, and the absolute amounts of the identified pre-rRNA and rRNA species in the nucleolus and nucleoplasm were determined. Characteristic changes in the pre-rRNA and rRNA pool sizes in regenerating liver are found which reveal alternations in both pre-rRNA processing and nucleocytoplasmic transition of ribosomes.

Animals↗
PubMed1982

Electron microscopic localization of silver staining NOR-proteins in rat liver nucleoli upon D-galactosamine block of transcription.

The method for electron microscopy of the Ag-staining of NOR-specific proteins was adapted to tissue sections from solid organs. The distribution of the Ag-staining proteins in rat liver nucleoli after complete block of transcription caused by D-galactosamine was investigated. In control animals, the Ag-staining proteins are associated with the fibrillar components of nucleoli. After block of transcription, positive Ag-staining is observed in the condensed fibrillar components of segregated nucleoli and later in the derived dense nucleolar fibrillar remnants. The granular components and the spherical bodies in segregated nucleoli are negative. It is concluded that in interphase nucleoli the Ag-staining NOR proteins are associated with the fibrillar components and with the derived nucleolar fibrillar remnants. The positive Ag-staining does not reflect the actual transcription of rRNA genes since it is present in both transcribed and non-transcribed r-chromatin.

Animals↗
PubMed1980

Ribosomal RNA precursor transcription in rat liver is not dependent on continuous synthesis of proteins.

The effect of inhibition of protein synthesis by cycloheximide on rRNA precursor transcription in rat liver was analyzed. Two doses of the drug were studied: low, 5 mg/kg, and high, 20 mg/kg. Both doses of cycloheximide cause rapid, complete and continuous inhibition of protein synthesis. The low dose of the antibiotic does not alter the rRNA precursor transcription for at least 4 h, while the high dose, which is lethal to rats, leads gradually to suppression of rRNA precursor synthesis. It is shown that the high dose of cycloheximide causes profound changes in the metabolism of the free nucleotides and drastic inhibition of [14C]orotate and [32P]orthophosphate uptake into the pool of free nucleotides. It is supposed that the strong side-effects of cycloheximide, rather than the cessation of protein synthesis, are responsible for the observed inhibition of rRNA precursor synthesis. It is concluded that rRNA precursor transcription is not regulated by rapidly turning-over protein(s).

Animals↗
PubMed1980

Maturation and nucleo-cytoplasmic transport of rat-liver ribosomal RNA upon D-galactosamine inhibition of transcription.

D-Galactosamine (250 mg/kg body weight) causes 90--95% inhibition of [14C]orotate or inorganic [32P]phosphate incorporation in vivo into rat liver nuclear RNA within 30 min. The transcription of both nucleolar and nucleoplasmic genes is inhibited to the same extent. Under these conditions, prelabbeled 45-S pre-rRNA is processed quantitatively to nuclear 28-S and 18-S rRNA. The nucleocytoplasmic transport of both 28-S and 18-S rRNA remains unaltered for about 60 min after blockage of transcription. At this stage the nucleo-cytoplasmic transport of 18-S rRNA is almost completed. It is concluded that formation and nucleo-cytoplasmic transport of ribosomes is independent of concurrent transcription of rRNA or nucleoplasmic genes. At later stages, the nucleocytoplasmic transport of 28-S rRNA is delayed and its partial degaradation in the nucleus may take place. This effect is correlated with a decreased (up to 40% of controls) labelling of nuclear proteins. However, the labelling of total cellular or microsomal proteins remains unchanged up to 3 h after D-galactosamine administration. It is suggested that the last nuclear steps of ribosome formation are dependent on the continuous supply of rapidly-labelled nuclear proteins.

Animals↗
PubMed1978

Quantitative analysis of rat liver nucleolar and nucleoplasmic ribosomal ribonucleic acids.

rRNA from detergent-purified nuclei was fractionated quantitatively, by two independent methods, into nucleolar and nucleoplasmic RNA fractions. The two RNA fractions were analysed by urea/agar-gel electrophoresis and the amount of pre-rRNA (precursor of rRNA) and rRNA components was determined. The rRNA constitutes 35% of total nuclear RNA, of which two-thirds are in nucleolar RNA and one-third in nucleoplasmic RNA. The identified pre-rRNA components (45 S, 41 S, 39 S, 36 S, 32 S and 21 S) are confined to the nucleolus and constitute about 70% of its rRNA. The remaining 30% are represented by 28 S and 18 S rRNA, in a molar ratio of 1.4. The bulk of rRNA in nucleoplasmic RNA is represented by 28 S and 18 S rRNA in a molar ratio close to 1.0. Part of the mature rRNA species in nucleoplasmic RNA originate from ribosomes attached to the outer nuclear membrane, which resist detergent treatment. The absolute amount of nuclear pre-rRNA and rRNA components was evaluated. The amount of 32 S and 21 S pre-rRNA (2.9 x 10(4) and 2.5 x 10(4) molecules per nucleus respectively) is 2-3-fold higher than that of 45 S, 41 S and 36 S pre-rRNA.

Animals↗
PubMed1978

Processing and migration of ribosomal ribonculeic acids in the nucleolus and nucleoplasm of rat liver nuclei.

Kinetic studies on the labelling in vivo with [14C]orotate of rat liver nucleolar and nucleoplasmic pre-rRNA (precursor of rRNA) and rRNA, isolated from detergent-purified nuclei, were carried out. The mathematical methods used for the computer analysis of specific-radioactivity curves are described. Evaluation of the experimental data permitted the selection of the most probable models for the processing of pre-rRNA and the nucleo-cytoplasmic transfer of rRNA. It was shown that considerable flexibility exists in the sequence of endonuclease attacks at critical sites of 45 and 41 S pre-rRNA chains, resulting in the simultaneous occurrence of several processing pathways. However, the phosphodiester bonds involved in the formation of mature 28 and 18 S rRNA appear to be protected until the generation of their immediate pre-rRNA. The turnover rates and half-lives of all pre-rRNA and rRNA pools were determined. The turnover rate of 45 S pre-rRNA corresponds to the formation of 1100 ribosomes/min per nucleus. The model for the nucleolus-nucleoplasm-cytoplasm migration of rRNA includes a 'nucleoplasm' compartment in which the small ribosomal subparticle is in rapid equilibrium with the respective cytoplasmic pool. At equimolar amounts of nuclear 28 and 18 S rRNA this model explains the faster appearance of labelled small ribosomal subparticles in the cytoplasm simultaneous with a lower labelling of nuclear 18 S rRNA as compared with 28 S rRNA.

Animals↗