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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/H1834    most recent 00435.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Tseng, Y.-T. Articles by Padbury, J. F. Search for Related Content PubMed PubMed Citation Articles by Tseng, Y.-T. Articles by Padbury, J. F.

Ontogeny of phosphoinositide 3-kinase signaling in developing heart: effect of acute -adrenergic stimulation

Department of Pediatrics, Women and Infants Hospital of Rhode Island, Brown Medical School, Providence, Rhode Island

Submitted 29 April 2005 ; accepted in final form 6 July 2005

Signaling pathways underlying transition of cardiomyocyte growth from hyperplasia in fetal/newborn to hypertrophy in postnatal/adult hearts are not well understood. We have shown that -adrenergic receptor (-AR)-mediated regulation of neonatal cardiomyocyte proliferation involves p70 ribosomal protein S6 kinase (p70S6K). Here we examined the ontogeny of phosphoinositide 3-kinase (PI3K)/p70S6K signaling pathway in rat hearts and investigated the influence of -AR on this pathway during development. Cardiac PI3K and p70S6K1 activities were high in the embryonic day 20 fetus, decreased gradually postnatally, and were low in the adult. In contrast, p70S6K2 was barely detectable. Phosphorylation of p70S6K1, Akt, and phosphoinositide-dependent protein kinase 1 were markedly increased in late gestation and early postnatal life but not in adult hearts. Phosphatase and tensin homolog on chromosome 10 (PTEN), a negative regulator of PI3K, was highly expressed in adult hearts but only at low levels and mostly in the phosphorylated (inactivated) form in the fetus. -AR stimulation resulted in increased cardiac p70S6K1 activity only in animals 2 wk old, whereas Akt level was increased in all developmental stages tested. These increases were accompanied by increased Bcl-2 associated death promoter (Ser136) phosphorylation without changes in PTEN level. Thus there is globally high input of cardiac PI3K signaling during the fetal-neonatal transition period. Inactivation of PTEN may in part contribute to the high activity of PI3K signaling, which coincides with the period of high cardiomyocyte proliferation. -AR stimulation activates cardiac p70S6K1 and Akt in postnatal animals and may activate cardiac survival signals. These data provide further evidence for the importance of -AR and PI3K signaling in the regulation of cardiac growth during development.

Akt; isoproterenol; phosphoinositide-dependent protein kinase 1; proliferation; phosphatase and tensin homolog on chromosome 10

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