Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle

Abstract

Poly(ADP-ribose) polymerase activity in nuclei isolated from differentiating cardiac muscle of the rat has been characterized and its activity measured during development. Optimum enzyme activity is observed at pH 8.5. Poly(ADP-ribose) polymerase is inhibited by ATP, thymidine, nicotinamide, theophylline, 3-isobutyl-1-methylxanthine and caffeine and stimulated by actinomycin D. The activity measured under optimal assay conditions increases during differentiation of cardiac muscle and is inversely related to the rate of DNA synthesis and to the activities of DNA polymerase alpha and thymidine kinase. When DNA synthesis and the activity of DNA polymerase alpha are inhibited in cardiac muscle of the 1-day-old neonatal rat by dibutyryl cyclic AMP or isoproterenol, the specific activity of poly(ADP-ribose) polymerase measured in isolated nuclei is increased. The concentration of NAD+ in cardiac muscle increases during postnatal development. In the adult compared with the 1-day-old neonatal rat the concentration of NAD+ relative to fresh tissue weight, DNA or protein increased 1.7-fold, 5.2-fold or 1.4-fold respectively. The concentration of NAD+ in cardiac muscle of the 1-day-old neonatal rat can be increased by approx. 20% by dibutyryl cyclic AMP. These data suggest that NAD+ and poly(ADP-ribose) polymerase may be involved with the repression of DNA synthesis and cell proliferation in differentiating cardiac muscle.

Localization and partial characterization of ADP-ribosylation products in hearts from adult and neonatal rats

“…Previous workers have reported both complementary and contradictory results concerning poly(ADP-ribose) polymerase activity. Claycomb [8] demonstrated that the activity of poly(ADP-ribose) polymerase in rat heart nuclei increased by about 2-fold between day 1 and day 16 of postnatal development and is even higher in the adult. In contrast, Jackowski & Kun [13] showed that the poly(ADP-ribose) polymerase activity of neonatal (5-day-old) cardiocyte nuclei is about 10 times greater than in nuclei of adult rats.…”

“…Several authors have also demonstrated the presence of poly(ADP-ribose) polymerase activity in rat cardiac muscle nuclei [8,9]. Several hormones, as well as circulatory stress (i.e.…”

“…The cardiomyocytes are not completely differentiated and continue to divide for several days after birth [14]. After the third week of postnatal development, the growth of the heart is primarily due to muscle cell enlargement and to some extent to the accumulation of nonmuscle cells [8]. The extracellular matrix composition [15] and the isoform of myosin heavy chain [16] are different in neonatal compared with adult heart.…”

The Involvement of ATP Produced via (ADP-Ribose)n in the Maintenance of DNA Replication Apparatus during DNA Repair

“…The concentration of nuclei was set at 1ϫ10 6 /tube. Incubation was carried out at 37°C for indicated times.…”

The expression of the [Bgl] genetic complex during preimplantation mouse embryogenesis and in ovulated eggs

“…Actinomycin D is also reported to have additional effects on cells not related to the suppression of RNA synthesis. First, it does affect DNA polymerase activity at levels of 2-10 Ug/ml in vitro (Hurwitz et , 1962 Of interest are reports that poly(adenosine diphosphate ribose) polymerase activity is affected by actinomycin D (Claycomb, 1976;Yoshihara, 1972 (Golbus, Calarco and Epstein, 1973;Levey, Troike and Brinster, 1977;Warner and Versteegh, 1974). At low dosages (1 ug/ml) its primary effect is suppression of the form I I RNA polymerase (Chambon, 1975).…”