This Article Full Text Full Text (PDF) Methods Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mende, U. Articles by Neer, E. J. Search for Related Content PubMed PubMed Citation Articles by Mende, U. Articles by Neer, E. J. Related Collections Cell signalling/signal transduction Genetically altered mice Heart failure - basic studies

(Circulation Research. 1999;85:1085.)
© 1999 American Heart Association, Inc.

Integrative Physiology

Signal Transduction in Atria and Ventricles of Mice With Transient Cardiac Expression of Activated G Protein _q

U. Mende, A. Kagen, M. Meister, E. J. Neer

From the Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Ulrike Mende, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail mende{at}calvin.bwh.harvard.edu

Abstract—We recently showed that the transient expression of a hemagglutinin (HA) epitope–tagged, constitutively active mutant of the G protein _q subunit (HA_q*) in the hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after HA_q* protein becomes undetectable. We demonstrated that the activity of phospholipase Cß, the immediate downstream target of activated G_q, is increased at 2 weeks, when HA_q* is expressed, but also at 10 weeks, when HA_q* is no longer detectable. This observation suggested that the transient HA_q* expression causes multiple, persistent changes in cellular signaling pathways. We now demonstrate changes in the level, activity, or both of several signaling components, including changes in the amount and hormone responsiveness of phospholipase Cß enzymes, in the basal level of diacylglycerol (which predominantly reflects activation of phospholipase D), in the amount or distribution of protein kinase C (PKC) isoforms (PKC, PKC, and PKC), and in the amount of several endogenous G proteins. These changes vary depending on the isoform of the signaling molecule, the chamber in which it is expressed, and the presence or absence of HA_q*. Our results suggest that a network of linked signaling functions determines the development of hypertrophy. They also suggest that atria and ventricles represent different signaling domains. It is likely that such changes occur in other model systems in which the activity of a single signaling component is increased, either due to an activating mutation or due to overexpression of the wild type.

Key Words: heart • hypertrophy • transgene • G protein • signal transduction

This article has been cited by other articles:

				M. Zhu, A. A. Gach, G. Liu, X. Xu, C. C. Lim, J. X. Zhang, L. Mao, K. Chuprun, W. J. Koch, R. Liao, et al. Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G{alpha}o* protein Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1335 - H1347. [Abstract] [Full Text] [PDF]

				M.-S. Kim, S. M. Lee, W. D. Kim, S. H. Ki, A. Moon, C. H. Lee, and S. G. Kim G{alpha}12/13 Basally Regulates p53 through Mdm4 Expression Mol. Cancer Res., May 1, 2007; 5(5): 473 - 484. [Abstract] [Full Text] [PDF]

				W. Zhang, T. Anger, J. Su, J. Hao, X. Xu, M. Zhu, A. Gach, L. Cui, R. Liao, and U. Mende Selective Loss of Fine Tuning of Gq/11 Signaling by RGS2 Protein Exacerbates Cardiomyocyte Hypertrophy J. Biol. Chem., March 3, 2006; 281(9): 5811 - 5820. [Abstract] [Full Text] [PDF]

				A. Sabri, B. A. Wilson, and S. F. Steinberg Dual Actions of the G{alpha}q Agonist Pasteurella multocida Toxin to Promote Cardiomyocyte Hypertrophy and Enhance Apoptosis Susceptibility Circ. Res., May 3, 2002; 90(8): 850 - 857. [Abstract] [Full Text] [PDF]

				K. Mier, D. Kemken, H. A. Katus, G. Richardt, and T. Kurz Adrenergic activation of cardiac phospholipase D: role of {alpha}1-adrenoceptor subtypes Cardiovasc Res, April 1, 2002; 54(1): 133 - 139. [Abstract] [Full Text] [PDF]

				G. Z. Feuerstein and D. Rozanski G Proteins and Heart Failure : Is G{alpha}q a Novel Target for Heart Failure? Circ. Res., December 8, 2000; 87(12): 1085 - 1086. [Full Text] [PDF]

				C. Ruwhof and A. van der Laarse Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways Cardiovasc Res, July 1, 2000; 47(1): 23 - 37. [Abstract] [Full Text] [PDF]

				A. Sabri, B. A. Wilson, and S. F. Steinberg Dual Actions of the G{alpha}q Agonist Pasteurella multocida Toxin to Promote Cardiomyocyte Hypertrophy and Enhance Apoptosis Susceptibility Circ. Res., May 3, 2002; 90(8): 850 - 857. [Abstract] [Full Text] [PDF]