Abstract
In rat neonatal myocytes, a constitutively active G alpha(q) causes cellular injury and apoptosis. However, stimulation of the alpha(1)-adrenergic receptor, one of the G(q) protein-coupled receptors, with phenylephrine for 48 h causes little cellular injury and apoptosis. Expression of the G beta gamma-sequestering peptide beta ARK-ct increases the phenylephrine-induced cardiac injury, indicating that G beta gamma released from G(q) counteracts the G alpha(q)-mediated cellular injury. Stimulation with phenylephrine activates extracellular signal-regulated kinase (ERK) and Akt, and activation is significantly blunted by beta ARK-ct. Inhibition of Akt by inhibitors of phosphatidylinositol 3-kinase increases the cellular injury induced by phenylephrine stimulation. In contrast to the inhibition of Akt, inhibition of ERK does not affect the phenylephrine-induced cardiac injury. These results suggest that G beta gamma released from G(q) upon alpha(1)-adrenergic receptor stimulation activates ERK and Akt. However, activation of Akt but not ERK plays an important role in the protection against the G alpha(q)-induced cellular injury and apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Apoptosis
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Carrier Proteins / pharmacology
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Cell Respiration / drug effects
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Cells, Cultured
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Enzyme Inhibitors / pharmacology
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GTP-Binding Protein alpha Subunits, Gq-G11
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GTP-Binding Protein beta Subunits*
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GTP-Binding Protein gamma Subunits*
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Heterotrimeric GTP-Binding Proteins / antagonists & inhibitors*
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Heterotrimeric GTP-Binding Proteins / genetics
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Kinetics
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Mitochondria / drug effects
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Mitochondria / physiology
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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Myocardium / cytology
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Myocardium / metabolism*
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Peptides*
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Phenylephrine / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Rats
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Rats, Sprague-Dawley
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Receptors, Adrenergic, alpha-1 / metabolism*
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Recombinant Proteins*
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Signal Transduction*
Substances
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Carrier Proteins
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Enzyme Inhibitors
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G-protein Beta gamma
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Peptides
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Proto-Oncogene Proteins
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Receptors, Adrenergic, alpha-1
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Recombinant Proteins
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beta-adrenergic receptor kinase inhibitory peptide
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Phenylephrine
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases
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GTP-Binding Protein alpha Subunits, Gq-G11
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Heterotrimeric GTP-Binding Proteins