title: Selective stimulation by tri-iodothyronine of myocardial deoxyribonucleic acid polymerase-alpha in neonatal rats.
abstract: 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.
mesh_terms: D000367:Age Factors; D000818:Animals; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D003853:Deoxyribonucleosides / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D003853:Deoxyribonucleosides; D014284:Triiodothyronine; D011189:Potassium Chloride; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase; D005033:Ethylmaleimide