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(The FASEB Journal. 2001;15:1921-1926.)
© 2001 FASEB

ß-Adrenergic receptors (ßAR) regulate cardiomyocyte proliferation during early postnatal life

YI-TANG TSENG1, RISHA KOPEL, JOAN P. STABILA, BETHANY G. MCGONNIGAL, TIEN T. NGUYEN, PHILIP A. GRUPPUSO* and JAMES F. PADBURY

Department of Pediatrics,
* Rhode Island Hospital, Women and Infants’ Hospital of Rhode Island, Brown Medical School, Providence, Rhode Island 02905, USA

1Correspondence: Department of Pediatrics, Women & Infants’ Hospital of RI, 101 Dudley St., Providence, RI 02905, USA. E-mail: Yi-Tang_Tseng{at}brown.edu

Cardiomyocyte development switches from hyperplasmic to hypertrophic growth between postnatal days 3 and 4 in rats. The mechanisms responsible for this transition have been controversial. ß-Adrenergic receptor (ßAR) activation of mitogenic responses in vitro has been reported. We hypothesized that tonic activation of the ßAR signaling regulates cell division in neonatal cardiomyocytes via effects on signaling kinases known to be important in cell cycle regulation. The purpose of the current study was to elucidate the roles of ßAR in rat cardiomyocyte growth in vivo. We demonstrated that ßAR blockade induced a significant reduction in cardiomyocyte proliferation as measured by the BrdU labeling index. Blockade of ßAR did not affect p38 or p44/42 MAPK activities. We further demonstrated that ßAR blockade induced a prompt deactivation of the p70 ribosomal protein S6 kinase (p70 S6K). To confirm these results, we measured p70 S6K activity directly. Basal activity of p70 S6K in neonatal cardiomyocytes was fourfold higher than that of insulin-treated adult rat liver. The activity of p70 S6K was reduced by 60% within 1 min after ßAR blockade. We conclude that the ßAR are involved in regulation of neonatal cardiomyocyte proliferation and that this mitogenic control may be mediated via the p70 S6K pathway.—Tseng, Y.-T., Kopel, R., Stabila, J. P., McGonnigal, B. G., Nguyen, T. T., Gruppuso, P. A., Padbury, J. F. ß-Adrenergic receptors (ßAR) regulate cardiomyocyte proliferation during early postnatal life.


Key Words: MAPK • p70 S6K • propranolol




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