{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T13:06:23Z","timestamp":1758891983401},"reference-count":34,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p>The phosphoinositide 3-kinase (PI3-kinase)-protein kinase B (Akt) signaling pathway is essential in the induction of physiological cardiac hypertrophy. In contrast, protein kinase C \u03b22 (PKC\u03b22) is implicated in the development of pathological cardiac hypertrophy and heart failure. Thus far, no clear association has been demonstrated between these two pathways. In this study, we examined the potential interaction between the PI3-kinase and PKC\u03b22 pathways by crossing transgenic mice with cardiac specific expression of PKC\u03b22, constitutively active (ca) PI3-kinase, and dominant-negative (dn) PI3-kinase. In caPI3-kinase\/PKC\u03b22 and dnPI3-kinase\/PKC\u03b22 double-transgenic mice, the heart weight-to-body weight ratios and cardiomyocyte sizes were similar to those observed in caPI3-kinase and dnPI3-kinase transgenic mice, respectively, suggesting that the regulation of physiological developmental hypertrophy via modulation of cardiomyocyte size proceeds through the PI3-kinase pathway. In addition, we observed that caPI3-kinase\/PKC\u03b22 mice showed improved cardiac function while the function of dnPI3-kinase\/PKC\u03b22 mice was similar to that of the PKC\u03b22 group. PKC\u03b22 protein levels in both dnPI3-kinase\/PKC\u03b22 and PKC\u03b22 mice were significantly upregulated. Interestingly, however, PKC\u03b22 protein expression was significantly attenuated in caPI3-kinase\/PKC\u03b22 mice. PI3-kinase activity measured by Akt phosphorylation was not affected by PKC\u03b22 overexpression. These data suggest a potential interaction between these two pathways in the heart, where PI3-kinase is predominantly responsible for the regulation of physiological developmental hypertrophy and may act as an upstream modulator of PKC\u03b22 with the potential for rescuing the pathological cardiac dysfunction induced by overexpression of PKC\u03b2.<\/jats:p>","DOI":"10.1152\/ajpheart.00562.2008","type":"journal-article","created":{"date-parts":[[2009,1,3]],"date-time":"2009-01-03T01:26:55Z","timestamp":1230946015000},"page":"H566-H572","source":"Crossref","is-referenced-by-count":21,"title":["Phosphoinositide 3-kinase Akt signaling pathway interacts with protein kinase C\u03b22 in the regulation of physiologic developmental hypertrophy and heart function"],"prefix":"10.1152","volume":"296","author":[{"given":"Debra 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