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Effects of norepinephrine on neonatal rat cardiocyte growth and differentiation

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Summary

Norepinephrine stimulates the growth in size of nondividing neonatal cardiocytes. During this time the neonatal cardiocyte is in a period of transition in which the cell can synthesize DNA and yet does not divide. Because the cell undergoes karyokinesis without cytokinesis the objective of this study was to determine whether the norepinephrine-induced growth in size of the neonatal cardiocyte was accompanied by an increase in a) the number of cardiocytes synthesizing DNA, b) the number of binucleate cardiocytes, and c) organized myofibrils. One- to four-d-old neonatal rat heart cells were isolated and placed in serum-free medium which was then supplemented with serum, norepinephrine, norepinephrine plus propranolol, or isoproterenol. After 4 d the number and size of the cells was determined using a Coulter counter. In other cultures cardiocytes were fixed on Days 0, 1, 2, and 4, and an increase in the number of binucleate cardiocytes was found in all treatment groups including controls. However, the rate of binucleation was faster in the norepinephrine group. It was also determined by proliferating cell nuclear antigen (PCNA) antibody staining that by Day 4, over 50% of the cardiocytes were in the cell cycle. The percentage of cells in which PCNA could be detected was higher in the norepinephrine and norepinephrine plus propranolol groups. Furthermore, there was a concomitant increase in the amount and organization of myofibrils in the catecholamine-treated cardiocytes.

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References

  • Anversa, P.; Olivetti, G.; Loud A. V. Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia and binucleation of myocytes. Cir. Res. 46:495–502; 1980.

    CAS  Google Scholar 

  • Baserga, R. Introduction to cell growth: growth in size and DNA replication. Handb. Exp. Pharmacol. 57:1–12; 1981.

    Google Scholar 

  • Bishopric, N. H.; Simpson, P. C.; Ordahl, C. P. Induction of the skeletal α-actin gene in α1 hypertrophy of rat cardiac myocytes. J. Clin. Invest. 80:1194–1199; 1987.

    PubMed  CAS  Google Scholar 

  • Blaes, N.; Boissel, J. Growth-stimulating effect of catecholamines on rat aortic smooth muscle cells in culture. J. Cell Physiol. 116:167–172; 1988.

    Article  Google Scholar 

  • Bravo, R.; Macdonald-Bravo, H. Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J. Cell Biol. 105:1549–1554; 1987.

    Article  PubMed  CAS  Google Scholar 

  • Bravo, R.; Blundell, P. A.; Macdonald-Bravo, H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-γ. Nature 326:515–517; 1987.

    Article  PubMed  CAS  Google Scholar 

  • Brodsky, W. Y.; Arefyeva, A. M.; Uryvaeva I. V. Mitotic polyploidization of mouse heart myocytes during the first postnatal week. Cell Tissue Res. 210:133–144; 1980.

    Article  PubMed  CAS  Google Scholar 

  • Bugaisky, L.; Zak, R. Biological mechanisms of hypertrophy. In: Fozzard, H. A.; Haber, E.; Jennings, R. B., et al. eds. The heart and cardiovascular system. New York; Raven Press: 1986:1491–1506.

    Google Scholar 

  • Clubb, F. J.; Bishop, S. P. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy. Lab. Invest. 50:571–577; 1984.

    PubMed  Google Scholar 

  • Connolly, J. A.; Sarabia, V. E.; Kelvin, D. J., et al. The disappearance of a cyclin-like protein and the appearance of statin is correlated with the onset of differentiation during myogenesis in vitro. Exp. Cell. Res. 174:461–471; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Cooper, G.; Mercer, W. E.; Hoober, J. K., et al. Load regulation of the properties of adult feline cardiocytes. The role of substrate adhesion. Circ. Res. 58:692–705; 1986.

    PubMed  Google Scholar 

  • Cruise, J. L.; Michalopoulos, G. Norepinephrine and epidermal growth factor: dynamics of their interaction in the stimulation of hepatocyte DNA synthesis. J. Cell. Physiol. 125:45–50; 1985.

    Article  PubMed  CAS  Google Scholar 

  • Cruise, J. L.; Houck, K. A.; Michalopoulos, G. K. Induction of DNA synthesis in cultured rat hepatocytes through stimulation of α1 by norepinephrine. Science 227:749–751; 1985.

    Article  PubMed  CAS  Google Scholar 

  • Gerdes, A. M.; Moore, J. A.; Hines, J. M., et al. Regional differences in myocyte size in normal rat heart. Anat. Rec. 215:420–426; 1986.

    Article  PubMed  CAS  Google Scholar 

  • Jaskulski, D.; Gatti, C.; Travali, S.; et al. Regulation of the proliferating cell nuclear antigen cyclin and thymidine kinase mRNA levels by growth factors. J. Biol. Chem. 263:10174–10179; 1988.

    Google Scholar 

  • Marino, T. A.; Kuseryk, L.; Lauva, I. K. Role of contraction in the structure and growth of neonatal rat cardiocytes. Am. J. Physiol. 253:H1391–1399; 1987.

    PubMed  CAS  Google Scholar 

  • Marino, T. A.; Kuseryk, L. Factors regulating neonatal cardiocyte growth in size and myofibrils. Anat. Rec. 218:88A; 1987.

    Article  Google Scholar 

  • Marino, T. A.; Walter, R. A.; D'Ambra, K., et al. The effects of catecholamines on fetal, rat cardiocytes in vitro. Am. J. Anat. 186:127–132; 1989.

    Article  PubMed  CAS  Google Scholar 

  • Meidell, R. S.; Sen, A.; Henderson, S. A., et al. α1 stimulation of rat myocardial cells increases protein synthesis. Am. J. Physiol. 251:H1076-H1084; 1986.

    PubMed  CAS  Google Scholar 

  • Olivetti, G.; Anversa, P.; Loud, A. V. Morphometric study of early postnatal development in left and right ventricular myocardium of the rat II. Tissue composition, capillary growth and sarcoplasmic alterations. Circ. Res. 46:503–512; 1980.

    PubMed  CAS  Google Scholar 

  • Prelich, G.; Kostura, M.; Marchak, D. R. et al. The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature 326:471–475; 1987a.

    Article  PubMed  CAS  Google Scholar 

  • Prelich, G.; Tan, C.; Kostura, M., et al. Functional identity of proliferating cell nuclear antigen and a DNA polymerase-γ auxiliary protein. Nature 326:517–520; 1987.

    Article  PubMed  CAS  Google Scholar 

  • Sherline, P.; Mascardo, R. Catecholamines are mitogenic in 3T3 and bovine aortic endothelial cells. J. Clin. Invest. 74:483–487; 1984.

    PubMed  CAS  Google Scholar 

  • Simpson, P. Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha, adrenergic response. J. Clin. Invest. 72:732–738; 1983.

    Article  PubMed  CAS  Google Scholar 

  • Simpson, P. Stimulation of hypertrophy of cultured neonatal rat heart cells through an α1 receptor and induction of beating through and α1 and α1 receptor interaction. Evidence for independent regulation of growth and beating. Circ. Res. 56:884–894; 1985.

    PubMed  CAS  Google Scholar 

  • Simpson, P.N.; Bishopric, N. S.; Coughlin, J. et al. Dual trophic effects of the alpha1-adrenergic receptor in cultured neonatal heart muscle cells. J. Mol. Cell. Cardiol. 18(Supplement 5): 45–58; 1986.

    Article  PubMed  CAS  Google Scholar 

  • Simpson, P.; McGrath, A.; Savion, S. Myocyte hypertrophy in neonatal rat heart cultures and its regulation by serum and by catecholamines. Circ. Res. 51:787–801; 1982.

    PubMed  CAS  Google Scholar 

  • Starksen, N. F.; Simpson, P. C.; Bishopric, N. et al. Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Proc. Natl. Acad. Sci. USA 83:8349–8350; 1986.

    Article  Google Scholar 

  • Tan, C.; Castillo, C.; So, A. G., et al. An auxiliary protein for DNA polymerase-γ from fetal calf thymus. J. Biol. Chem. 26:12310–12316; 1986.

    Google Scholar 

  • Ueno, H. Perryman, M. B.; Roberts, R., et al. Differentiation of cardiac myocytes after mitogen withdrawal exhibits three sequential states of the ventricular growth response. J. Cell Biol. 107:1911–1918; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Zak, R. Factors controlling cardiac growth. In: Zak, R., ed Growth of the heart in health and disease. New York: Raven Press; 1984:165–185.

    Google Scholar 

  • Zuber, M.; Tan, E. M.; Ryoji, M. Involvement of proliferating cell nuclear antigen (cyclin) in DNA replication in living cells. Mol. Cell. Biol. 9:57–66; 1989.

    PubMed  CAS  Google Scholar 

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Supported in part by grant No. HL 29351 from the National Institutes of Health, by a grant from the American Heart Association and with the support of the Southeastern Pennsylvania and Pennsylvania Affiliates of the American Heart Association.

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Marino, T.A., Walter, R.A., Cobb, E. et al. Effects of norepinephrine on neonatal rat cardiocyte growth and differentiation. In Vitro Cell Dev Biol 26, 229–236 (1990). https://doi.org/10.1007/BF02624452

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