Modifications of major aspects of myocardial ribonucleic acid metabolism as a response to noradrenaline. Action of the hormone on cytoplasmic processing of ribonucleic acid after reserpine treatment

Treatment of perfused rabbit heart with reserpine causes a decrease of incorporation of labelled precursors into RNA species of subcellular fractions and polyamines. Ornithine decarboxylase, S-adenosylmethionine decarboxylase and cytoplasmic Mn2+-stimulated polyadenylate polymerase activities are not modified. Addition of noradrenaline to reserpine-treated perfused hearts enhances, compared with the control, the incorporation of precursor into RNA in all subcellular fractions other than the nuclear one, restores incorporation of labelled putrescine into polyamines, enhances ornithine decarboxylase and S-adenosylmethionine decarboxylase activities and causes a 12-fold increase in cytoplasmic Mn2+-dependent polyadenylate polymerase activity. After treatment with noradrenaline the increase in radioactivity was found solely in AMP after hydrolysis of microsomal RNA to nucleoside monophosphates.

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Regulation of ribonucleic acid synthesis by polyamines. Reversal by spermine of inhibition by methylglyoxal bis(guanylhydrazone) of ribonucleic acid synthesis and histone acetylation in rabbit heart

Biochemical Journal ◽

10.1042/bj1520091 ◽

1975 ◽

Vol 152 (1) ◽

pp. 91-98 ◽

Cited By ~ 27

Author(s):

C M Caldarera ◽

A Casti ◽

C Guarnier ◽

G Moruzzi

Keyword(s):

Histone Acetylation ◽

Ribonucleic Acid ◽

Specific Radioactivity ◽

Acid Synthesis ◽

Rabbit Heart ◽

Decarboxylase Activity ◽

Perfused Heart ◽

Rna Transcription ◽

Adenosylmethionine Decarboxylase ◽

The Relationship

The relationship between polyamines and RNA synthesis was studied by considering the action of spermine on histone acetylation in perfused heart. In addition, the effect of methylglyoxal bis(guanylhydrazone), inhibitor of putrescine-activated S-adenosylmethionine decarboxylase activity, on RNA and polyamine specific radioactivity and on acetylation of histone fractions was also investigated in perfused heart. Different concentrations of spermine and/or methylglyoxas bis(guanylhydrazone) were injected into the heart, 15 min after beginning the perfusion. The results demonstrate that spermine stimulates the specific radioactivity of RNA of subcellular fractions. Acetylation of the arginine-rich histone fractions, involved in the regulation of RNA transcription, is enhanced by spermine. The perfusion with methylglyoxal bis(guanylhydrazone) causes a decrease in the specific radioactivity of polyamines and RNA, and in acetylation of histone fractions. However, spermine is able to reverse the methylglyoxal bis(guanylhydrazone) inhibition when injected simultaneously. From these results we may assume a possible role for spermine in the regulation of RNA transcription.

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Overproduction of cardiac S-adenosylmethionine decarboxylase in transgenic mice

Biochemical Journal ◽

10.1042/bj20051196 ◽

2005 ◽

Vol 393 (1) ◽

pp. 295-302 ◽

Cited By ~ 17

Author(s):

Oleg Nisenberg ◽

Anthony E. Pegg ◽

Patricia A. Welsh ◽

Kerry Keefer ◽

Lisa M. Shantz

Keyword(s):

Transgenic Mice ◽

Ornithine Decarboxylase ◽

Fold Increase ◽

Adrenergic Stimulation ◽

Compensatory Mechanisms ◽

Specific Expression ◽

Adenosylmethionine Decarboxylase ◽

Cardiac Phenotype ◽

Founder Line ◽

Do So

The present study was designed to provide a better understanding of the role played by AdoMetDC (S-adenosylmethionine decarboxylase), the key rate-controlling enzyme in the synthesis of spermidine and spermine, in controlling polyamine levels and the importance of polyamines in cardiac physiology. The αMHC (α-myosin heavy chain) promoter was used to generate transgenic mice with cardiac-specific expression of AdoMetDC. A founder line (αMHC/AdoMetDC) was established with a >100-fold increase in AdoMetDC activity in the heart. Transgene expression was maximal by 1 week of age and remained constant into adulthood. However, the changes in polyamine levels were most pronounced during the first week of age, with a 2-fold decrease in putrescine and spermidine and a 2-fold increase in spermine. At later times, spermine returned to near control levels, whereas putrescine and spermidine levels remained lower, suggesting that compensatory mechanisms exist to limit spermine accumulation. The αMHC/AdoMetDC mice did not display an overt cardiac phenotype, but there was an increased cardiac hypertrophy after β-adrenergic stimulation with isoprenaline (‘isoproterenol’), as well as a small increase in spermine content. Crosses of the αMHC/AdoMetDC with αMHC/ornithine decarboxylase mice that have a >1000-fold increase in cardiac ornithine decarboxylase were lethal in utero, presumably due to increase in spermine to toxic levels. These findings suggest that cardiac spermine levels are highly regulated to avoid polyamine-induced toxicity and that homoeostatic mechanisms can maintain non-toxic levels even when one enzyme of the biosynthetic pathway is greatly elevated but are unable to do so when two biosynthetic enzymes are increased.

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Modifications of major aspects of myocardial ribonucleic acid metabolism as a response to noradrenaline. Behaviour of polyadenylate polymerase and ribonucleic acid polymerase, acetylation of histones and rate of synthesis of polyamines

Biochemical Journal ◽

10.1042/bj1680333 ◽

1977 ◽

Vol 168 (3) ◽

pp. 333-340 ◽

Cited By ~ 9

Author(s):

A Casti ◽

A Corti ◽

N Reali ◽

G Mezzetti ◽

G Orlandini ◽

...

Keyword(s):

Cyclic Amp ◽

Ribonucleic Acid ◽

Acid Metabolism ◽

Specific Radioactivity ◽

Rabbit Heart ◽

Polymerase Activity ◽

Dibutyryl Cyclic Amp ◽

General Increase ◽

Stimulation Of

Noradrenaline added to perfused rabbit heart previously perfused with labelled precursors causes, after 2.5 and 5.0 min, a general increase of specific radioactivity or RNA in subcellular fractions, but no augmentation of acetylation of F2a2 and F2a1 histone fractions and no stimulation of DNA-dependent RNA polymerase activities. Synthesis of spermidine and spermine is enhanced at 10.0 min of treatment, when there is also a fall in specific radioactivity of RNA. The cytoplasmic Mn2+-stimulated polyadenylate polymerase activity is strongly enhanced 30s to 2.5 min after injection of noradrenaline or of dibutyryl cyclic AMP. Both the cyclic nucleotide and noradrenaline have no influence in vitro on the polyadenylate polymerase reaction.

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Genotoxicity and Cell Proliferative Activity of 3-Chloro-4-(Dichloromethyl)-5-Hydroxy-2(5H)-Furanone [MX] in Rat Glandular Stomach

Water Science & Technology ◽

10.2166/wst.1992.0311 ◽

1992 ◽

Vol 25 (11) ◽

pp. 341-345 ◽

Cited By ~ 38

Author(s):

C. Furihata ◽

M. Yamashita ◽

N. Kinae ◽

T. Matsushima

Keyword(s):

Cell Proliferation ◽

Body Weight ◽

Dna Synthesis ◽

Ornithine Decarboxylase ◽

Tap Water ◽

Fold Increase ◽

Single Strand ◽

Glandular Stomach ◽

Decarboxylase Activity ◽

Pyloric Mucosa

MX is a strong direct acting mutagen on Salmonella typhimurium TA100 and is present in chlorinated tap water which contains organic compounds. MX was administered orally to 7-week-old male F344 rats, and its geno-toxicity in the pyloric mucosa of stomach was examined by analysis of DNA single strand scissions by the alkaline elution method. The effect of MX on cell proliferation was examined by assays of the inductions of replicative DNA synthesis and ornithine decarboxylase. MX at closes of 20-48 mg/kg body weight induced DNA single strand scissions dose-dependently (p<0.02) in the pyloric mucosa of the stomach 2 h after its administration. Moreover at doses of 10-60 mg/kg body weight, it induced up to 21-fold increase in replicative DNA synthesis (p<0.01) 16 h after its administration. At doses of 10-60 mg/kg body weight, it induced up to 100-fold increase in ornithine decarboxylase activity with a maximum 16 h after its administration. These results suggest that MX is genotoxic and induces cell proliferation in the glandular stomach of rats.

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