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

Ribosomes are integral constitutens of the protein synthesis machinery. Polymerase I (POL I) is located in the nucleolus and transcribes the large ribosomal genes. POL I activity is decreased in ischemia but nothing is known so far on POL I in perinatal asphyxia. We investigated the involvement of POL I in a well-documented model of graded systemic asphyxia at the level of activity, mRNA, protein, and morphology. Caeserean section was performed at the 21st day of gestation. Rat pups still in the uterus horns were immerged in a water bath for asphyctic periods from 5-20 min. Brain was taken for measurement of pH, nuclear POL I activity, and mRNA steady state, and protein levels of RPA40, an essential subunit of POL I and III. Silver staining and transmission electron microscopy with morphometry when appropriate were used to examine the nucleolus. Brain pH and nuclear POL I activity decreased with the length of the asphyctic period while POL-I mRNA and protein levels were unchanged. Accompanying the decrease in brain pH we found significant changes of nucleolar structure in the course of perinatal asphyxia at the light and electron microscopic level. As early as ten min following the asphyctic insult, morphological disintegration of the nucleolus was observed. The changes became more dramatic with longer duration of perinatal asphyxia. We conclude that severe acidosis may be responsible for decreased POL activity and for disintegration of nucleoli in neurons. This condition may lower the ribosome content in neonatal neurons and impair protein synthesis.

[1]  N. Cairns,et al.  Decreased transcription factor junD in brains of patients with Down syndrome , 1998, Neuroscience Letters.

[2]  G. Längst,et al.  TTF‐I determines the chromatin architecture of the active rDNA promoter , 1998, The EMBO journal.

[3]  Q. Gai,et al.  Protein kinase C inhibits transcription from the RNA polymerase III promoter of the human c-myc gene. , 1998, Cancer letters.

[4]  H. Hoeger,et al.  Deficient transcription of subunit RPA 40 of RNA polymerase I and III in heart of rats with neonatal asphyxia. , 1997, Life sciences.

[5]  H. Hoeger,et al.  Transcription and activity of antioxidant enzymes after ionizing irradiation in radiation-resistant and radiation-sensitive mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[6]  G. Lubec,et al.  Decrease of brain protein kinase C, protein kinase A, and cyclin-dependent kinase correlating with pH precedes neuronal death in neonatal asphyxia. , 1997, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[7]  H. Hoeger,et al.  Decrease of heart protein kinase C and cyclin‐dependent kinase precedes death in perinatal asphyxia of the rat , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  G. Längst,et al.  RNA polymerase I transcription on nucleosomal templates: the transcription termination factor TTF‐I induces chromatin remodeling and relieves transcriptional repression , 1997, The EMBO journal.

[9]  J. Węsierska‐Gądek,et al.  Nuclear architecture and ultrastructural distribution of poly(ADP-ribosyl)transferase, a multifunctional enzyme. , 1996, Journal of cell science.

[10]  H. Forssberg,et al.  Early [18F]FDG positron emission tomography in infants with hypoxic‐ischaemic encephalopathy shows hypermetabolism during the postasphyctic period , 1995, Acta paediatrica.

[11]  J. Parks,et al.  Developmental Changes in Newborn Lamb Brain Mitochondrial Activity and Postasphyxial Lipid Peroxidation , 1995, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[12]  P. Cook,et al.  Site of transcription of ribosomal RNA and intranucleolar structure in HeLa cells. , 1994, Journal of cell science.

[13]  K. Smetana,et al.  Cytochemistry of satellite nucleoli in human lymphocytes. , 1993, Acta histochemica.

[14]  M. Derenzini,et al.  Distribution of DNA in human Sertoli cell nucleoli. , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[15]  L. Lindner Improvements in the silver-staining technique for nucleolar organizer regions (AgNOR). , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[16]  F. Wachtler,et al.  The uptake of uridine in the nucleolus occurs in the dense fibrillar component. Immunogold localization of incorporated digoxigenin-UTP at the electron microscopic level. , 1993, Cytogenetics and cell genetics.

[17]  D. Hernandez-Verdun,et al.  Revealing nucleolar architecture by low ionic strength treatment. , 1992, Experimental cell research.

[18]  T N Raju,et al.  Some animal models for the study of perinatal asphyxia. , 1992, Biology of the neonate.

[19]  H. E. Morgan,et al.  Phorbol ester stimulation of protein kinase C activity and ribosomal DNA transcription. Role in hypertrophic growth of cultured cardiomyocytes. , 1991, The Journal of biological chemistry.

[20]  T. Kerppola,et al.  RNA polymerase: regulation of transcript elongation and termination , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  P. Zahradka,et al.  Control points in eucaryotic ribosome biogenesis. , 1991, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[22]  P. Hozák,et al.  In situ separation of nucleolar components by hypotonic treatment of cells , 1990, Biology of the cell.

[23]  L. Andersen Number, volume and size distribution of nucleoli in rat neurosecretory cells with suppressed and stimulated secretion. , 1990, Acta anatomica.

[24]  L. Chuang,et al.  Isolation and purification of protein kinase C from human leukemia ML-1 cells phosphorylation of human leukemia RNA polymerase II in vitro. , 1989, Biochimica et biophysica acta.

[25]  E. Geiduschek,et al.  Transcription by RNA polymerase III. , 1988, Annual review of biochemistry.

[26]  H. Imura,et al.  Triiodothyronine effects on RNA polymerase activities in isolated neuronal and glial nuclei of the mature rat brain cortex. , 1987, Metabolism: Clinical and Experimental.

[27]  J. Tower,et al.  Transcription of cloned eukaryotic ribosomal RNA genes. , 1986, Annual review of biochemistry.

[28]  G. Dienel,et al.  Temporal Profiles of Proteins Responsive to Transient Ischemia , 1985, Journal of neurochemistry.

[29]  A. Sentenac Eukaryotic RNA polymerases. , 1985, CRC critical reviews in biochemistry.

[30]  B. White,et al.  Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. , 1982, The Journal of biological chemistry.

[31]  S. Jacob,et al.  Activation of purified hepatoma RNA polymerase I by homologous protein kinase NII. , 1981, The Journal of biological chemistry.

[32]  M. Chavko,et al.  Effect of Ischemia on the Activity of DNA‐Dependent RNA Polymerase and DNA Polymerase , 1981, Journal of neurochemistry.

[33]  S. Jacob,et al.  Protein kinase activity of RNA polymerase I purified from a rat hepatoma: probable function of Mr 42,000 and 24,600 polypeptides. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[34]  W. Pulsinelli,et al.  Regional Protein Synthesis in Rat Brain Following Acute Hemispheric Ischemia , 1980, Journal of neurochemistry.

[35]  I B Dawid,et al.  Repeated genes in eukaryotes. , 1980, Annual review of biochemistry.

[36]  T. Yanagihara,et al.  Experimental stroke in gerbils: Effect on translation and transcription , 1978, Brain Research.

[37]  O. Jänne,et al.  Progesterone-regulated changes in transcriptional events in rabbit uterus. , 1977, Biochimica et biophysica acta.

[38]  K. Hossmann,et al.  THE EFFECT OF ISCHAEMIA AND RECIRCULATION ON PROTEIN SYNTHESIS IN THE RAT BRAIN , 1977, Journal of neurochemistry.

[39]  J. Mauck Solubilized DNA-dependent RNA polymerase activities in resting and growing fibroblast. , 1977, Biochemistry.

[40]  O. Martelo,et al.  Phosphorylation of rat liver ribonucleic acid polymerase I by nuclear protein kinases. , 1976, The Journal of biological chemistry.

[41]  A. Hadjiolov,et al.  Maturation of ribosomal ribonucleic acids and the biogenesis of ribosomes. , 1976, Progress in biophysics and molecular biology.

[42]  P. Chambon Eukaryotic nuclear RNA polymerases. , 1975, Annual review of biochemistry.

[43]  P. Chambon 9. Eucaryotic RNA Polymerases , 1974 .

[44]  R. Rodnight,et al.  Research Methods in Neurochemistry , 2013, Springer US.

[45]  B. McEwen,et al.  Isolation of Brain Cell Nuclei , 1972 .

[46]  B. Hallgren,et al.  THE EFFECT OF AGE ON THE NON‐HAEMIN IRON IN THE HUMAN BRAIN , 1958, Journal of neurochemistry.

[47]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.