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. 1987 Oct;80(4):1194–1199. doi: 10.1172/JCI113179

Induction of the skeletal alpha-actin gene in alpha 1-adrenoceptor-mediated hypertrophy of rat cardiac myocytes.

N H Bishopric 1, P C Simpson 1, C P Ordahl 1
PMCID: PMC442365  PMID: 2821075

Abstract

Myocardial hypertrophy in vivo is associated with reexpression of contractile protein isogenes characteristic of fetal and neonatal development. The molecular signals for hypertrophy and isogene switching are unknown. We studied alpha (sarcomeric)-actin messenger RNA (mRNA) expression in cultured cardiac myocytes from the neonatal rat. In the cultured cells, as in the adult heart in vivo, expression of cardiac alpha-actin (cACT) predominated over that of skeletal alpha-actin (sACT) mRNA, the fetal/neonatal isoform. alpha 1-Adrenergic receptor stimulation induced hypertrophy of these cells, increasing total RNA and cytoskeletal actin mRNA by 1.8-fold over control, and total alpha-actin mRNA by 4.3 fold. This disproportionate increase in total alpha-actin mRNA was produced by a preferential induction of sACT mRNA, which increased by 10.6-fold over control versus only 2.6-fold for cACT mRNA. The alpha 1-adrenoceptor is the first identified molecular mediator of early developmental isogene reexpression in cardiac myocyte hypertrophy.

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Selected References

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  1. Auffray C., Nageotte R., Chambraud B., Rougeon F. Mouse immunoglobulin genes: a bacterial plasmid containing the entire coding sequence for a pre-gamma 2a heavy chain. Nucleic Acids Res. 1980 Mar 25;8(6):1231–1241. doi: 10.1093/nar/8.6.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevan J. A. Norepinephrine and the presynaptic control of adrenergic transmitter release. Fed Proc. 1978 Feb;37(2):187–190. [PubMed] [Google Scholar]
  3. Blaes N., Boissel J. P. Growth-stimulating effect of catecholamines on rat aortic smooth muscle cells in culture. J Cell Physiol. 1983 Aug;116(2):167–172. doi: 10.1002/jcp.1041160207. [DOI] [PubMed] [Google Scholar]
  4. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cruise J. L., Houck K. A., Michalopoulos G. K. Induction of DNA synthesis in cultured rat hepatocytes through stimulation of alpha 1 adrenoreceptor by norepinephrine. Science. 1985 Feb 15;227(4688):749–751. doi: 10.1126/science.2982212. [DOI] [PubMed] [Google Scholar]
  6. Cutilletta A. F. Myosin heavy chain mRNA during the development and regression of myocardial hypertrophy. Eur Heart J. 1984 Dec;5 (Suppl F):193–197. doi: 10.1093/eurheartj/5.suppl_f.193. [DOI] [PubMed] [Google Scholar]
  7. Cutilletta A. F., Rudnik M., Zak R. Muscle and non-muscle cell RNA polymerase activity during the development of myocardial hypertrophy. J Mol Cell Cardiol. 1978 Aug;10(8):677–687. doi: 10.1016/0022-2828(78)90403-0. [DOI] [PubMed] [Google Scholar]
  8. Everett A. W., Sinha A. M., Umeda P. K., Jakovcic S., Rabinowitz M., Zak R. Regulation of myosin synthesis by thyroid hormone: relative change in the alpha- and beta-myosin heavy chain mRNA levels in rabbit heart. Biochemistry. 1984 Apr 10;23(8):1596–1599. doi: 10.1021/bi00303a002. [DOI] [PubMed] [Google Scholar]
  9. Exton J. H. Mechanisms involved in alpha-adrenergic phenomena. Am J Physiol. 1985 Jun;248(6 Pt 1):E633–E647. doi: 10.1152/ajpendo.1985.248.6.E633. [DOI] [PubMed] [Google Scholar]
  10. Flink I. L., Rader J. H., Morkin E. Thyroid hormone stimulates synthesis of a cardiac myosin isozyme. Comparison of the two-two-dimensional electrophoretic patterns of the cyanogen bromide peptides of cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits. J Biol Chem. 1979 Apr 25;254(8):3105–3110. [PubMed] [Google Scholar]
  11. Gunning P., Ponte P., Blau H., Kedes L. alpha-skeletal and alpha-cardiac actin genes are coexpressed in adult human skeletal muscle and heart. Mol Cell Biol. 1983 Nov;3(11):1985–1995. doi: 10.1128/mcb.3.11.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gustafson T. A., Markham B. E., Morkin E. Analysis of thyroid hormone effects on myosin heavy chain gene expression in cardiac and soleus muscles using a novel dot-blot mRNA assay. Biochem Biophys Res Commun. 1985 Aug 15;130(3):1161–1167. doi: 10.1016/0006-291x(85)91737-1. [DOI] [PubMed] [Google Scholar]
  13. Hirzel H. O., Tuchschmid C. R., Schneider J., Krayenbuehl H. P., Schaub M. C. Relationship between myosin isoenzyme composition, hemodynamics, and myocardial structure in various forms of human cardiac hypertrophy. Circ Res. 1985 Nov;57(5):729–740. doi: 10.1161/01.res.57.5.729. [DOI] [PubMed] [Google Scholar]
  14. Izumo S., Lompré A. M., Matsuoka R., Koren G., Schwartz K., Nadal-Ginard B., Mahdavi V. Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals. J Clin Invest. 1987 Mar;79(3):970–977. doi: 10.1172/JCI112908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klein I., Hong C. Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart. J Clin Invest. 1986 May;77(5):1694–1698. doi: 10.1172/JCI112488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Korecky B., Rakusan K. Normal and hypertrophic growth of the rat heart: changes in cell dimensions and number. Am J Physiol. 1978 Feb;234(2):H123–H128. doi: 10.1152/ajpheart.1978.234.2.H123. [DOI] [PubMed] [Google Scholar]
  17. Mahdavi V., Lompre A. M., Chambers A. P., Nadal-Ginard B. Cardiac myosin heavy chain isozymic transitions during development and under pathological conditions are regulated at the level of mRNA availability. Eur Heart J. 1984 Dec;5 (Suppl F):181–191. doi: 10.1093/eurheartj/5.suppl_f.181. [DOI] [PubMed] [Google Scholar]
  18. Minty A. J., Alonso S., Caravatti M., Buckingham M. E. A fetal skeletal muscle actin mRNA in the mouse and its identity with cardiac actin mRNA. Cell. 1982 Aug;30(1):185–192. doi: 10.1016/0092-8674(82)90024-1. [DOI] [PubMed] [Google Scholar]
  19. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  20. Ordahl C. P. The skeletal and cardiac alpha-actin genes are coexpressed in early embryonic striated muscle. Dev Biol. 1986 Oct;117(2):488–492. doi: 10.1016/0012-1606(86)90315-5. [DOI] [PubMed] [Google Scholar]
  21. Ordahl C. P., Tilghman S. M., Ovitt C., Fornwald J., Largen M. T. Structure and developmental expression of the chick alpha-actin gene. Nucleic Acids Res. 1980 Nov 11;8(21):4989–5005. doi: 10.1093/nar/8.21.4989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ostman-Smith I. Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci (Lond) 1981 Sep;61(3):265–272. doi: 10.1042/cs0610265. [DOI] [PubMed] [Google Scholar]
  23. Paterson B. M., Eldridge J. D. alpha-Cardiac actin is the major sarcomeric isoform expressed in embryonic avian skeletal muscle. Science. 1984 Jun 29;224(4656):1436–1438. doi: 10.1126/science.6729461. [DOI] [PubMed] [Google Scholar]
  24. Rossi M. A., Carillo S. V. Does norepinephrine play a central causative role in the process of cardiac hypertrophy? Am Heart J. 1985 Mar;109(3 Pt 1):622–624. doi: 10.1016/0002-8703(85)90582-4. [DOI] [PubMed] [Google Scholar]
  25. Schwartz K., de la Bastie D., Bouveret P., Oliviéro P., Alonso S., Buckingham M. Alpha-skeletal muscle actin mRNA's accumulate in hypertrophied adult rat hearts. Circ Res. 1986 Nov;59(5):551–555. doi: 10.1161/01.res.59.5.551. [DOI] [PubMed] [Google Scholar]
  26. Sheer D., Morkin E. Myosin isoenzyme expression in rat ventricle: effects of thyroid hormone analogs, catecholamines, glucocorticoids and high carbohydrate diet. J Pharmacol Exp Ther. 1984 Jun;229(3):872–879. [PubMed] [Google Scholar]
  27. Sherline P., Mascardo R. Catecholamines are mitogenic in 3T3 and bovine aortic endothelial cells. J Clin Invest. 1984 Aug;74(2):483–487. doi: 10.1172/JCI111445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Simpson P. Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response. J Clin Invest. 1983 Aug;72(2):732–738. doi: 10.1172/JCI111023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Simpson P. Stimulation of hypertrophy of cultured neonatal rat heart cells through an alpha 1-adrenergic receptor and induction of beating through an alpha 1- and beta 1-adrenergic receptor interaction. Evidence for independent regulation of growth and beating. Circ Res. 1985 Jun;56(6):884–894. doi: 10.1161/01.res.56.6.884. [DOI] [PubMed] [Google Scholar]
  30. Starksen N. F., Simpson P. C., Bishopric N., Coughlin S. R., Lee W. M., Escobedo J. A., Williams L. T. Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8348–8350. doi: 10.1073/pnas.83.21.8348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sugden D., Vanecek J., Klein D. C., Thomas T. P., Anderson W. B. Activation of protein kinase C potentiates isoprenaline-induced cyclic AMP accumulation in rat pinealocytes. 1985 Mar 28-Apr 3Nature. 314(6009):359–361. doi: 10.1038/314359a0. [DOI] [PubMed] [Google Scholar]
  32. Swynghedauw B., Moalic J. M., Bouveret P., Bercovici J., de la Bastie D., Schwartz K. Messenger RNA content and complexity in normal and overloaded rat heart: a preliminary report. Eur Heart J. 1984 Dec;5 (Suppl F):211–217. doi: 10.1093/eurheartj/5.suppl_f.211. [DOI] [PubMed] [Google Scholar]
  33. Tarazi R. C., Sen S., Saragoca M., Khairallah P. The multifactorial role of catecholamines in hypertensive cardiac hypertrophy. Eur Heart J. 1982 Apr;3 (Suppl A):103–110. doi: 10.1093/eurheartj/3.suppl_a.103. [DOI] [PubMed] [Google Scholar]
  34. Thomas P. S. Hybridization of denatured RNA transferred or dotted nitrocellulose paper. Methods Enzymol. 1983;100:255–266. doi: 10.1016/0076-6879(83)00060-9. [DOI] [PubMed] [Google Scholar]
  35. Zakut R., Shani M., Givol D., Neuman S., Yaffe D., Nudel U. Nucleotide sequence of the rat skeletal muscle actin gene. Nature. 1982 Aug 26;298(5877):857–859. doi: 10.1038/298857a0. [DOI] [PubMed] [Google Scholar]

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