In vivo pressure overload hypertrophy induces phosphoinositide 3-kinase activation that is Gbetagamma-dependent, with Gbetagamma dimers arising from stimulation of G(q)-coupled receptors.
This study demonstrates that in vivo pressure overload hypertrophy activates phosphoinositide 3-kinase via a Gbetagamma-dependent process originating from G(q)-coupled receptors.
Activation of phosphoinositide 3-kinases is coupled to both phosphotyrosine/growth factor and G protein-coupled receptors. We explored the role of phosphoinositide 3-kinase activation in myocardium during in vivo pressure overload hypertrophy in mice. Cytosolic extracts from wild type hypertrophied hearts showed a selective increase in the phosphoinositide 3-kinase gamma isoform. To address the role of G protein-coupled receptor-mediated activation of phosphoinositide 3-kinase, we used transgenic mice with cardiac-specific overexpression of a Gbetagamma sequestering peptide. Extracts from hypertrophied transgenic hearts showed complete loss of phosphoinositide 3-kinase activation, indicating a Gbetagamma-dependent process. To determine the class of G proteins that contribute Gbetagamma dimers for in vivo phosphoinositide 3-kinase activation, two strategies were used: 1) transgenic mice with cardiac-specific overexpression of a G(q) inhibitor peptide and 2) pertussis toxin treatment prior to pressure overload in wild type mice. Pressure overloaded G(q) inhibitor transgenic mice showed a complete absence of phosphoinositide 3-kinase activation, whereas pretreatment with pertussis toxin showed robust phosphoinositide 3-kinase activation. Taken together, these data demonstrate that activation of the phosphoinositide 3-kinase during in vivo pressure overload hypertrophy is Gbetagamma-dependent and the Gbetagamma dimers arise from stimulation of G(q)-coupled receptors.
Prasad et al. (Tue,) conducted a other in In vivo pressure overload hypertrophy. Transgenic overexpression of Gbetagamma sequestering peptide, G(q) inhibitor peptide, or pertussis toxin vs. Wild type mice / no inhibitor was evaluated on Phosphoinositide 3-kinase activation. In vivo pressure overload hypertrophy induces phosphoinositide 3-kinase activation that is Gbetagamma-dependent, with Gbetagamma dimers arising from stimulation of G(q)-coupled receptors.