Studies on the Isolation and Biosynthesis of Macromolecular Ribonucleic Acid in the Brain

Nievel, John G.; Kirby, K.S.

doi:10.1042/bj1010007c

Cited by 21 publications

(6 citation statements)

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“…In fact, histological studies of these cells led Valentin to propose the term nucleolus in 1839. Metabolic labeling studies confirmed that neuronal nucleoli contain active RNAPol1 (Nievel & Kirby 1966;Lovtrup-Rein & Grahn 1970;Stoykova et al 1979Stoykova et al , 1983. The possibility that neuronal nucleolar transcription serves as a sensor of DNA damage is supported by observations of nucleolar dysfunction/disorganization in dorsal root ganglia (DRG) neurons from rodents treated with DNA damaging anti-cancer drugs including cisplatin, other Pt derivatives and the DNA topoisomerase-1 (Topo1) inhibitor doxorubicin (Tomiwa et al 1986;Bigotte & Olsson 1987;McKeage et al 2001;Jamieson et al 2005).…”

Section: Nucleolar Stress As a Neurotoxic Consequence Of Dna Damagementioning

confidence: 94%

“…In mammalian brain, the portion of the mRNA‐coding genome that is transcribed is 3–5 times greater than elsewhere in the body (Hahn & Laird 1971; Bantle & Hahn 1976). Also, robust rRNA synthesis has been detected in both developing and adult rat brain neurons and glia (Nievel & Kirby 1966; Lovtrup‐Rein & Grahn 1970; Stoykova et al 1979, 1983). Transcriptional inhibitors applied to various animal models have revealed the importance of transcription for the physiology of the nervous system including long‐term synaptic plasticity, learning and memory, or completion of developmental cell death (Matthies 1989; Matthies et al 1990; Oppenheim et al 1990).…”

Section: Functions Of Transcriptionmentioning

confidence: 99%

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Neurotoxic mechanisms of DNA damage: focus on transcriptional inhibition

Hetman

Vashishta

Rempała

2010

Journal of Neurochemistry

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J. Neurochem. (2010) 114, 1537–1549. Abstract Although DNA damage‐induced neurotoxicity is implicated in various pathologies of the nervous system, its underlying mechanisms are not completely understood. Transcription is a DNA transaction that is highly active in the nervous system. In addition to its direct role in expression of the genetic information, transcription contributes to DNA damage detection and repair as well as chromatin organization including biogenesis of the nucleolus. Transcription is inhibited by DNA single‐strand breaks and DNA adducts. Hence, transcription inhibition may be an important contributor to the neurotoxic consequences of such types of DNA damage. This review discusses the existing evidence in support of the latter hypothesis. The presented literature suggests that neuronal DNA damage interferes with the RNA‐Polymerase‐2‐dependent transcription of genes encoding proteins with critical functions in neurotransmission and intracellular signaling. The latter category includes extracellular signal‐regulated kinase‐1/2 mitogen‐activated protein kinase phosphatases whose lowered expression results in chronic activation of extracellular signal‐regulated kinase‐1/2 and its reduced responsiveness to physiological stimuli. Conversely, DNA damage‐induced inhibition of RNA‐Polymerase‐1 and the subsequent disruption of the nucleolus induce p53‐mediated apoptosis of developing neurons. Finally, decreasing nucleolar transcription may link DNA damage to chronic neurodegeneration in adults.

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Section: Nucleolar Stress As a Neurotoxic Consequence Of Dna Damagementioning

confidence: 94%

Section: Functions Of Transcriptionmentioning

confidence: 99%

Neurotoxic mechanisms of DNA damage: focus on transcriptional inhibition

Hetman

Vashishta

Rempała

2010

Journal of Neurochemistry

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“…Changes in the fate of radioactive glucose carbon in the brain amino acids after administration of the electric current may reflect the increased activity state of the biphasic reaction of brain to electroshock. Under identical conditions, however, no effect on RNA synthesis was observed in spite of the fact that some species of macromolecular RNA in brain turn over at high rate (Nievel & Kirby, 1966) and synthesis of 'pulselabelled' RNA in brain is generally expected to change with altered behaviour. Overall changes in the functional activities of the brain may also be reflected in the distribution and staining properties (Einarson, 1932;Hyden, 1943) or the function of the Nissl substances (Nievel & Cumings, 1967), which are composed of free and protein-bound ribosomal aggregates, synthesizing protein at a high rate.…”

mentioning

confidence: 96%

“…The individual amino acids were further separated by paper chromatography. In experiments to assess 562nd MEETING, BANGOR RNA extracted with hot HClO, or phenol (Nievel & Kirby, 1966).…”

mentioning

confidence: 99%

Compartmentation of Amino Acids and Change in the Fate of Radioactive Glucose in Rat Brain after Electroshock and Reserpine Pretreatment

Nievel

1976

Biochemical Society Transactions

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Mn2+ had about 25 % the activity of Mgz+. With Mgz+ in excess, ADP activated the kinase up to 5-fold as measured by colorimetric or radiotracer assay. With ATP at 5 mM and Mg2+ at 15 m, activity increased with ADP up to 5 mM. If phosphoenolpyruvate plus pyruvate kinase were added to controls, reconverting ADP into ATP, their activity was decreased and an %fold stimulation of activity by ADP was observed. Stimulation was due to an increase in the Vmax. for the reaction rather than a decrease in the K,,, for either ATP or the substrate. It was noted that high concentrations of ATP relative to ADP often decreased the kinase activity, even with excess of Mgz+ present. The ratio of coenzyme to effector appeared to be important and the effect of varying the molar ratio [ATP]/([ATP]+ [ADP]) on activity was measured at various total nucleotide concentrations. Curves similar to that shown in Fig. 2 were obtained. These results show that Pseuabmonus sp. N.C.I.B. 8858 contains an ATP-l-aminopropan-2-01 phosphotransferase, the L-isomer being the preferred substrate. Modulation of activity by ADP (and ATP) indicates a catabolic role for the kinase, probably in aminoacetone catabolism. A biosynthetic role in phospholipid formation has been postulated for an analogous enzyme from rat liver mitochondria (Willetts, 1974), which in contrast is unaffected by ADP, Mg2+ or EDTA and is virtually inactive with ethanolamine.

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“…Developmental Psychobiology, l(3): 189-195 (1968) the brain of rats (Appel, 1967;Jacob, Stevenin, Jund, Judes & Mandel, 1966;La Torre & Tandler, 1967;Nievel & Kirby, 1966), mice (Herriman & Hunter, 1965) and rabbits (Vesco & Giuditta, 1967). A series of properties of messenger RNA (mRNA) such as the incorporation of labelled precursors into the structure of mRNA, the base content, and the template activity manifesting itself by the stimulation of protein synthesis in cell-free system, was investigated.…”

mentioning

confidence: 99%

Synthesis of rapidly‐labelled brain RNA in the rat during stagnant hypoxia in the course of ontogeny

Sirakova

Sirakov

Jílek

et al. 1968

Developmental Psychobiology

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SIRAKOVA, I. A., SIRAKOV, L. M., J~L E K , L., and RYCHL~K, I. (19138). Synthesis of Rapidly-lnbelled Brain R N A in the R a t During StagizantHypoxia in the Course of Ontogeny. DEVELOPMENTAL PsucilosroLocu, I(3): 189-195. T h e nucleic acids of the cytoplasmic and nuclear fraction of the brain honiogenate were isolated by phenol procedure then were fractionated on a linear sucrose density gradient. T h e in vivo incorporation of [3H]-uridine into different types of RNA and the template activity of these nucleic acid fractions in control and hypoxic animals were studied in vitro in a cell-free protein synthetic system of E. coli. In adult animals, as in 25-day-old rats, stagnant hypoxia decreases the total synthesis of rapidly-labelled RNA in nuclei and impairs the template activity in cytoplasm. In 12-day-old rats, the synthesis of rapidly-labelled RNA does not change in stagnant hypoxia and the template activity increases mainly in the low molecular weight fractions. Metabolic adaptation of immature nervous tissue to hypoxia involves specific changes of protein and nucleic acid metabolism as well as in carbohydrate and energy metabolism.

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Studies on the Isolation and Biosynthesis of Macromolecular Ribonucleic Acid in the Brain

Cited by 21 publications

References 6 publications

Neurotoxic mechanisms of DNA damage: focus on transcriptional inhibition

Neurotoxic mechanisms of DNA damage: focus on transcriptional inhibition

Compartmentation of Amino Acids and Change in the Fate of Radioactive Glucose in Rat Brain after Electroshock and Reserpine Pretreatment

Synthesis of rapidly‐labelled brain RNA in the rat during stagnant hypoxia in the course of ontogeny

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