Thymidine kinase activity in cardiac muscle during embryonic and postnatal development

Gillette, Paul C.; Claycomb, William C.

doi:10.1042/bj1420685

Cited by 28 publications

(6 citation statements)

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“…We have re-examined these issues (Limas & Limas, 1978) by separately determining the activity of three DNA polymerases (x, ,B and ;P) from muscle and non-muscle cells of the developing myocardium. Decline in muscle cell polymerases was much less (30 40 % compared with day 1) than previous studies (Doyle et al, 1974;Gillette & Claycomb, 1974;Claycomb, 1975;Hubscher et al, 1977;Claycomb, 1977) have indicated and occurred entirely within the first 2 weeks of post-natal life; non-muscle-cell polymerases were essentially unchanged when expressed as [3H]dTMP/106 cells. (b) DNA polymerase activities in quiescent cells cannot predict the ability of the cells to proliferate in response to stimuli.…”

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confidence: 63%

“…The implication (Claycomb, 1976), however, that this decline is responsible for the restriction in proliferative capacity of myocardial cells is complicated by two considerations. (a) None of the reported studies (Doyle et al, 1974;Gillette & Claycomb, 1974;Claycomb, 1975Claycomb, , 1976Hubscher et al, 1977;Claycomb, 1977) has taken into consideration that myocardial cell size increases considerably during early post-natal growth (Sasaki et al, 1968;Katzberg et al, 1977) and that expression of enzymic activity per mg of protein may grossly overestimate the magnitude of DNA polymerase decline. The cellular heterogeneity of the heart has also been ignored, despite the fact that non-muscle (interstitial and endothelial) cells retain their proliferative capacity to adulthood (Morkin & Ashford, 1968; Grove et al, 1969).…”

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confidence: 99%

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Selective stimulation by tri-iodothyronine of myocardial deoxyribonucleic acid polymerase-α in neonatal rats

Limas

1979

Biochemical Journal

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Three forms of DNA polymerase (alpha, beta and gamma) were separated from isolated rat myocardial cells on the basis of template, pH and ionic requirements, sensitivity to N-ethylmaleimide and position on sucrose gradients. Tri-iodothyronine administration (20mug/100g intraperitoneally) to 3-week-old rats resulted in selective stimulation of DNA polymerase-alpha (198+/-7.1 versus 102+/-5.8pmol of [(3)H]dTMP/30min per mg of protein in untreated controls, P<0.01), with no change in polymerases-beta and -gamma. [(3)H]Thymidine incorporation into myocardial DNA was also enhanced in tri-iodothyronine-treated neonatal rats (132+/-11.2 versus 53+/-4.1c.p.m./mug of DNA in controls, P<0.001). Increased incorporation was associated with an expansion of deoxyribonucleoside 5'-triphosphate pools, especially that of dTTP (24+/-1.6 versus 10+/-1.1pmol/mg of DNA, P<0.01). Neither DNA polymerase activities nor [(3)H]thymidine incorporation were changed in 6-month-old rats in response to tri-iodothyronine. Unstimulated adult myocardial cells had DNA polymerase activities comparable with those in 3-week-old animals, but significantly lower [(3)H]-thymidine incorporation and deoxyribonucleoside triphosphate concentrations. Enhancement of both DNA polymerase-alpha activity and [(3)H]thymidine incorporation in tri-iodothyronine-treated young rats was prevented by concomitant administration of either vinblastine (1mug/g) or daunomycin (2mug/g); actinomycin D (0.1mug/g) or cycloheximide (8mug/g), on the other hand, prevented the increase in [(3)H]thymidine incorporation, but not DNA polymerase-alpha activation. These results demonstrate an age-dependent stimulation of myocardial DNA replication by tri-iodothyronine and suggest an inter-relationship between DNA synthesis and subsequent entry into mitosis.

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Selective stimulation by tri-iodothyronine of myocardial deoxyribonucleic acid polymerase-α in neonatal rats

Limas

1979

Biochemical Journal

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“…DNA polymerase has been found to accurately reflect myocardial cell proliferative activity (6,9,10). Cardiac DNA polymerase activity not only has been characterized (5), but this enzyme as well as another myocardial replicative enzyme, thymidine kinase, have correlated with [3H]thymidine incorporation as an indicator of ventricular mitotic activity (5,14). Moreover, we have used autoradiography in this study to verify that DNA polymerase activity reflects cardiac muscle cell division in both the control and 6-OHDtreated rats.…”

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confidence: 90%

Effect of Chemical Sympathectomy on Myocardial Cell Division in the Newborn Rat

et al. 1980

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Summarychemical sympathectomy on myocardial cell division in the newborn rat. Myocardial chemical sympathectomy was achieved by daily SC injection of 100 pg/g body weight of dOHdopamine to each of 239 Holtzman newborn rat pups for the first seven days of life. MATERIALS AND METHODS Effective sympathectomy was verified by identifying a decrease inChemical sympathectomy was accomplished by the administraventricular myocardial norepinephrine concentrations to 31% 2 12 tion of 6-hydroxydopamine (6-OHD) to newborn rat pups. The S.E. of control at 20 days of age. Activity of DNA polymerase was activity of DNA polymerase in the ventricular homogenate was used to indicate the extent of myocardial cell division.used to indicate the extent of ventricular myocardial cell division. Beginning at eight days of age, DNA polymerase activity was increased in the sympathectomized pups relative to control. The CHEMICAL SYMPATHECTOMY TECHNIQUE DNA polymerase activity was highest relative to control at 16 days (235% 2 31 S.E.) and remained elevated beyond 20 days A 481 HO1tzman W1) newborn rat pups were (188% + 30 of control). The DNA polymerase data was analyzed used in lhe There were 242 pups and 239 by covariance and was significantly greater in the 6-OHdopamine PUPS. A group four Or six pregnant rats was received every rat pups (P < 0.001).other wk. Each group of litters had nearly the same birth date (within 24 hr), and the sizes of the litters were equalized by Speculation transferring pups from large to small litters. The litters from onehalf of each group were used for control, and the other one-half Myocardial cell division continues for 10 to 14 days after birth was used for the daily SC administration of 6-OHD (Sigma in the newborn animal of several species, and the cell division then Chemical Co., St. Louis, MO). For example, if one group consisted ceases by an unknown mechanism. Our findings are consistent of four litters, each pup from two litters was given an injection of with the hypothesis that this postnatal decrease in myocardial cell 0.1 ml of 0.001 N NaC1, and each pup from the other two litters division is related to the development of cardiac sympathetic nerve was given an injection at the same time with 0.1 ml of 6-OHD ingrowth. Because nerve ingrowth was inhibited after 6-OHdo-(100 yg/g body weight of 6-OHD dissolved in 0.001 N NaCI). pamine and increased myocardial cell division occurred, it appears Because of the rapid deactivation of dissolved 6-OHD, it was that sympathetic ingrowth indeed may play a key role in affecting administered to the pups within 5 min after dissolving. Injection myocardial cell division in the newborn animal.was made into the loose skin of the nape within 24 hr after birth and repeated once daily for 7 days. These techniques were repeated for each of 22 groups of litters. The regulation of cardiac muscle cell division remains a complexIn both the control and experimental groups of rats, DNA problem (1,6,10,16,20,(24)(25)(26). Studies in the rat have shown polymerase and ventricula...

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“…DNA synthesis and hence cell proliferation in terminally differentiating cardiac muscle of the rat decrease progressively after birth and essentially cease by the middle of the third week of postnatal development (Claycomb, 1973(Claycomb, , 1975a. Temporally correlated with this loss in synthetic activity is an almost complete loss in activity of DNA polymerase a and thymidine kinase (Claycomb, 1973(Claycomb, , 1975aGillette & Claycomb, 1974>. The activity of DNA polymerase remains relatively constant during postnatal development (Claycomb, 1975a).…”

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

Claycomb

1976

Biochemical Journal

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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.

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Thymidine kinase activity in cardiac muscle during embryonic and postnatal development

Cited by 28 publications

References 21 publications

Selective stimulation by tri-iodothyronine of myocardial deoxyribonucleic acid polymerase-α in neonatal rats

Selective stimulation by tri-iodothyronine of myocardial deoxyribonucleic acid polymerase-α in neonatal rats

Effect of Chemical Sympathectomy on Myocardial Cell Division in the Newborn Rat

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

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