Brain RNA polymerase and nucleolar structure in perinatal asphyxia of the rat

Mosgoeller, Wilhelm; Kastner, Philomena; Fang-Kircher, S; Kitzmueller, Erwin; Hoeger, Harald; Seither, Peter; Labudova, Olga; Lubec, Barbara

doi:10.1203/00006450-199906000-00154

Cited by 5 publications

(9 citation statements)

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“…The situation is similar in pachytene of meiosis in which the DF is reduced and the FCs remain attached to the NOR chromosomes (Stahl et al, 1991). In perinatal asphyxia of the rat the nucleoli (of brain cells) show a marked disintegration of the strands of the DF corresponding to a decreased production of ribosomes (Mosgoeller et al, 2000;see Fig. 4) All these results suggest that the FCs are attached to the chromosomal NOR and act as a primer for any initiation or increased activity in ribosome biogenesis.…”

Section: Changes Of Nucleolar Morphology With Changes Of Functionmentioning

confidence: 49%

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Ribosome biogenesis in man: Current views on nucleolar structures and function

Schwarzacher¹,

Mosgoeller²

2000

Cytogenet Genome Res

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Nucleoli develop when preribosomes are synthesized at the chromosomal nucleolar organizer regions. Typically they consist of at least three nucleolar subcompartments, the fibrillar center (FC), the dense fibrillar component (DF), and the granular component (GC). The understanding of the functional arrangements of these subcompartments relates to aspects in cell biology, pathology, and virus research. In the present review morphological studies are discussed in the light of molecular findings. The available data confirm the hypothesis that rDNA transcription is connected with the DF but not necessarily with the presence of an FC. Within the DF, rDNA transcription is restricted to foci, possibly representing single transcribing genes. FCs may serve to store inactive transcription factors, to initiate rDNA transcription, and may provide structural support for transcription. The GC can be interpreted as a collection of maturing preribosomes. More recently the nucleolar subcompartments were focused on in the context of virus research and tumor biology.

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Section: Changes Of Nucleolar Morphology With Changes Of Functionmentioning

confidence: 49%

“…It appears to correlate with malignant cell activity and proliferation rate, hence it may provide an estimate of the prognosis in neoplastic diseases (Trere, 2000). Another application is the demonstration of a reduced nucleolar activity in perinatal asphyxia (Mosgoeller et al, 2000;see Fig. 4).…”

Section: Silver Stainingmentioning

confidence: 99%

Ribosome biogenesis in man: Current views on nucleolar structures and function

Schwarzacher¹,

Mosgoeller²

2000

Cytogenet Genome Res

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“…In a previous study, we showed deterioration of RNA polymerase and nucleolar changes within minutes after PA (17). Here, we show that deficient POL I activity along with decreased essential POL subunit PAF53 protein and disintegration of nucleolar structures still can be detected 8 d after the asphyctic insult.…”

Section: Discussionmentioning

confidence: 88%

“…It is also unclear whether deficient or disintegrated PAF53 would have contributed to impaired POL I activity, as Hanada et al (39) have shown that it is rather involved in the formation of the initiation complex at the promoter by mediating the interaction between POL I and UBF, the upstream binding factor for active rRNA synthesis. Decreased immunoreactive PAF53 in asphyctic brain samples may therefore help to explain decreased RNA, which was described in neurons to persist until at least 3 mo after PA (17). Decreased POL I activity along with decreased PAF53 may well cause decreased RNA in the postasphyctic period.…”

mentioning

confidence: 99%

“…In a recent report using a simple, well-documented, and noninvasive model of PA that resembles the clinical situation (15,16), we have shown that the POL I system in PA was affected as soon as within minutes after the asphyctic insult (17). It was the aim of this study to show whether this finding would be transient or persisting, and we indeed observed that POL derangement as reflected by decreased POL activity, an impaired POL subunit at the immunohistochemical and nucleolar disintegration at the electron microscopy level, was found approximately a week after the asphyctic insult.…”

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confidence: 99%

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Deficient Brain RNA Polymerase and Altered Nucleolar Structure Persists until Day 8 after Perinatal Asphyxia of the Rat

Kastner

2003

Pediatric Research

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[P.S.] RNA polymerases (POL) are integral constituents of the protein synthesis machinery, with POL I and POL III coding for ribosomal RNA and POL II coding for protein. POL I is located in the nucleolus and transcribes class I genes, those that code for large ribosomal RNA. It has been reported that the POL system is seriously affected in perinatal asphyxia (PA) immediately after birth. Because POL I is necessary for protein synthesis and brain protein synthesis was shown to be deranged after hypoxicischemic conditions, we aimed to study whether POL derangement persists in a simple, well-documented animal model of graded global PA at the activity, mRNA, protein, and morphologic level until 8 d after the asphyctic insult. Nuclear POL I activity was determined according to a radiochemical method; mRNA steady state and protein levels of RPA4O-an essential subunit of POL I and III-were evaluated by blotting methods; and the POL I subunit polymerase activating factor-53 was evaluated using immunohistochemistry. Silver staining and transmission electron microscopy were used to examine the nucleolus. At the eighth day after PA, nuclear POL I decreased with the length of the asphyctic period, whereas mRNA and protein levels for RPA4O were unchanged. The subunit polymerase activating factor-53, however, was unambiguously reduced in several brain regions. Dramatic changes of nucleolar morphology were observed, the main finding being nucleolar disintegration at the electron microscopy level. We suggest that severe acidosis and/or deficient protein kinase C in the brain during the asphyctic period may be responsible for disintegration of the nucleolus as well as for decreased POL activity persisting until the eighth day after PA. The biologic effect may be that PA causes impaired RNA and protein synthesis, which has been already observed in hypoxic-ischemic states. In eukaryotes, three different POL transcribe nuclear genes. POL I transcribes class I genes, those that code for large ribosomal RNA (rRNA). It is located in the nucleolus, represents 50 -70% of polymerase activity per cell, and as many as 40,000 copies per cell are present (1). This high number of POL I molecules transcribes as few as about 100 genes, which is appropriate as the rRNA precursor is long (i.e. 6,000 -15,000 nucleotides), and as many as 50 polymerase molecules may transcribe each rRNA gene simultaneously. This intense transcriptional activity reflects the need of the cell for rRNA; 10 million copies of rRNA are required (2) to form the 10 million ribosomes required for a single cell division. rRNA genes, transcribed by POL I, form the primary RNA transcript, the 45S-rRNA. Before release from the nucleus as ribosomal particles, 45S-rRNA is cleaved to a copy of 28S-rRNA, 18S-rRNA, and 5.8S-rRNA each. POL III transcribes class III genes, those that encode a number of small RNA molecules, including 5S-rRNA. It is located in the nucleoplasm, makes up 10% of the polymerase activity of the cell, and about 20,000 copies are present per cell (3). These...

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Plasticity of basal ganglia neurocircuitries following perinatal asphyxia: effect of nicotinamide

et al. 2007

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The potential neuroprotection of nicotinamide on the consequences of perinatal asphyxia was investigated with triple organotypic cultures. Perinatal asphyxia was induced in vivo by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Sibling caesarean-delivered pups were used as controls. Three days later tissue from substantia nigra, neostriatum and neocortex was dissected and placed on a coverslip. After a month, the cultures were processed for immunocytochemistry and phenotyped with markers against the NMDA receptor subunit NR1, tyrosine hydroxylase (TH), or neuronal nitric oxide synthase (nNOS). Some cultures were analysed for cell viability. Nicotinamide (0.8 mmol/kg, i.p.) or saline was administered to asphyxia-exposed and caesarean-delivered control pups 24, 48 and 72 h after birth. Perinatal asphyxia produced a decrease of cell viability in substantia nigra, but not in neostriatum or neocortex. Immunocytochemistry confirmed the vulnerability of the substantia nigra, demonstrating that there was a significant decrease in the number of NR1 and TH-positive (+) cells/mm2, as well as a decrease in the length of TH+ processes, suggesting neurite atrophy. In control cultures, many nNOS+ cells were seen, with different features, regional distribution and cell body sizes. Following perinatal asphyxia, there was an increase in the number of nNOS+ cells/mm2 in substantia nigra, versus a decrease in neostriatum including reduced neurite length, and no apparent changes in neocortex. The main effect of nicotinamide was seen in the neostriatum, preventing the asphyxia-induced decrease in the number of nNOS+ cells and neurite length. Nicotinamide also prevented the effect of perinatal asphyxia on TH-positive neurite length. The present results support the idea that nicotinamide can prevent the effects produced by a sustained energy-failure condition, as occurring during perinatal asphyxia.

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Brain RNA polymerase and nucleolar structure in perinatal asphyxia of the rat

Cited by 5 publications

References 0 publications

Ribosome biogenesis in man: Current views on nucleolar structures and function

Ribosome biogenesis in man: Current views on nucleolar structures and function

Deficient Brain RNA Polymerase and Altered Nucleolar Structure Persists until Day 8 after Perinatal Asphyxia of the Rat

Plasticity of basal ganglia neurocircuitries following perinatal asphyxia: effect of nicotinamide

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