G-proteins in growth and apoptosis: lessons from the heart
- 26 March 2001
- journal article
- review article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 20 (13), 1626-1634
- https://doi.org/10.1038/sj.onc.1204275
Abstract
The acute contractile function of the heart is controlled by the effects of released nonepinephrine (NE) on cardiac adrenergic receptors. NE can also act in a more chronic fashion to induce cardiomyocyte growth, characterized by cell enlargement (hypertrophy), increased protein synthesis, alterations in gene expression and addition of sarcomeres. These responses enhance cardiomyocyte contractile function and thus allow the heart to compensate for increased stress. The hypertrophic effects of NE are mediated through Gq-coupled α1-adrenergic receptors and are mimicked by the actions of other neurohormones (endothelin, prostaglandin F2α angiotensin II) that also act on Gq-coupled receptors. Activation of phospholipase C by Gq is necessary for these responses, and protein kinase C and MAP kinases have also been implicated. Gq stimulated cardiac hypertrophy is also evident in transgenic mouse models. In contrast, stimulation of Gs-coupled β-adrenergic receptors or Gi-coupled receptors do not directly effect cardiomyocyte hypertrophy. Apoptosis is also induced by G-protein-coupled receptor stimulation in cardiomyocytes. Sustained or excessive activation of either Gq- or Gs-signaling pathways results in apoptotic loss of cardiomyocytes both in vitro and in vivo. Apoptosis is associated with decreased ventricular function in the failing heart. Cardiomyocytes provide an ideal model system for understanding the basis for G-protein mediated hypertrophy and apoptosis, and the mechanisms responsible for the transition from compensatory to deleterious levels of signaling. This information may prove critical for designing interventions that prevent the pathophysiological consequences of heart failure.Keywords
This publication has 104 references indexed in Scilit:
- Gelsolin Binding and Cellular Presentation of Lysophosphatidic AcidPublished by Elsevier BV ,2000
- Cardiovascular α1-adrenoceptor subtypes: functions and signalingCanadian Journal of Physiology and Pharmacology, 2000
- RGS4 causes increased mortality and reduced cardiac hypertrophy in response to pressure overloadJCI Insight, 1999
- β-Adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic Gsα mouseJCI Insight, 1999
- Chronic ET A Receptor Blockade Attenuates Cardiac Hypertrophy Independently of Blood Pressure Effects in Renovascular Hypertensive RatsHypertension, 1999
- Targeting the Receptor-G q Interface to Inhibit in Vivo Pressure Overload Myocardial HypertrophyScience, 1998
- Dissociation of p44 and p42 Mitogen-activated Protein Kinase Activation from Receptor-induced Hypertrophy in Neonatal Rat Ventricular MyocytesPublished by Elsevier BV ,1996
- Prostaglandin F2α Stimulates Hypertrophic Growth of Cultured Neonatal Rat Ventricular MyocytesPublished by Elsevier BV ,1996
- Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes.JCI Insight, 1995
- Phorbol esters induce immediate-early genes and activate cardiac gene transcription in neonatal rat myocardial cellsJournal of Molecular and Cellular Cardiology, 1990