Phosphoinositide 3-kinase Akt signaling pathway interacts with protein kinase Cbeta2 in the regulation of physiologic developmental hypertrophy and heart function
| Autor: | Tetsuo Shioi, Julie R. McMullen, Debra L. Rigor, Peter M. Kang, Dmitry Ter-Ovanesyan, Jun H. Choi, Li Zhang, Zhiheng He, Seigo Izumo, George L. King, Soochan Bae, Natalya Bodyak |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Physiology Protein Kinase C beta Cardiomegaly Mice Transgenic Biology Ventricular Function Left Muscle hypertrophy Rats Sprague-Dawley Mice Phosphatidylinositol 3-Kinases Heart Rate Physiology (medical) Internal medicine medicine Animals Myocytes Cardiac Phosphorylation Protein kinase A Protein kinase B Protein kinase C Cells Cultured Protein Kinase C Cell Size Kinase Translational Physiology Heart Myocardial Contraction Rats Protein Subunits Endocrinology Mutation Cattle Female Signal transduction Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 296(3) |
| ISSN: | 0363-6135 |
| Popis: | 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 beta2 (PKCbeta2) 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 PKCbeta2 pathways by crossing transgenic mice with cardiac specific expression of PKCbeta2, constitutively active (ca) PI3-kinase, and dominant-negative (dn) PI3-kinase. In caPI3-kinase/PKCbeta2 and dnPI3-kinase/PKCbeta2 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/PKCbeta2 mice showed improved cardiac function while the function of dnPI3-kinase/PKCbeta2 mice was similar to that of the PKCbeta2 group. PKCbeta2 protein levels in both dnPI3-kinase/PKCbeta2 and PKCbeta2 mice were significantly upregulated. Interestingly, however, PKCbeta2 protein expression was significantly attenuated in caPI3-kinase/PKCbeta2 mice. PI3-kinase activity measured by Akt phosphorylation was not affected by PKCbeta2 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 PKCbeta2 with the potential for rescuing the pathological cardiac dysfunction induced by overexpression of PKCbeta. |
| Databáze: | OpenAIRE |
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