RGS4 reduces contractile dysfunction and hypertrophic gene induction in Gαq overexpressing mice

Jason H Rogers, Anna Tsirka, Attila Kovacs, Kendall J. Blumer, Gerald W. Dorn, Anthony J. Muslin

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The intrinsic GTPase activity of Gαq is low, and RGS proteins which activate GTPase are expressed in the heart: however, their functional relevance in vivo is unknown. Transgenic mice with cardiac-specific overexpression of Gαq in myocardium exhibit cardiac hypertrophy, enhanced PKCε membrane translocation, embryonic gene expression, and depressed cardiac contractility. We recently reported that transgenic mice with cardiac-specific expression of RGS4, a Gαq and Gαi GTPase activator, exhibit decreased left ventricular hypertrophy and ANF induction in response to pressure overload. To test the hypothesis that RGS4 can act as a Gαq-specific GTPase activating protein (GAP) in the in vivo heart, dual transgenic Gαq-40xRGS4 mice were generated to determine if RGS4 co-expression would ameliorate the Gαq-40 phenotype. At age 4 weeks, percent fractional shortening was normalized in dual transgenic mice as was left ventricular internal dimension and posterior and septal wall thicknesses. PKCε membrane translocation and ANF and α-skeletal actin mRNA levels were also normalized. Compound transgenic mice eventually developed depressed cardiac contractility that was evident by 9 weeks of age. These studies establish for the first time a role for RGS4 as a GAP for Gαq in the in vivo heart, and demonstrate that its regulated expression can have pathophysiologic consequences.

Original languageEnglish (US)
Pages (from-to)209-218
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume33
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Transgenic Mice
GTPase-Activating Proteins
GTP Phosphohydrolases
Atrial Natriuretic Factor
Genes
GTP Phosphohydrolase Activators
RGS Proteins
Membranes
Cardiomegaly
Left Ventricular Hypertrophy
Actins
Myocardium
Phenotype
Gene Expression
Pressure
Messenger RNA

Keywords

  • Cardiac hypertrophy
  • G protein
  • RGS
  • Signal transduction
  • Transgenic mice

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

RGS4 reduces contractile dysfunction and hypertrophic gene induction in Gαq overexpressing mice. / Rogers, Jason H; Tsirka, Anna; Kovacs, Attila; Blumer, Kendall J.; Dorn, Gerald W.; Muslin, Anthony J.

In: Journal of Molecular and Cellular Cardiology, Vol. 33, No. 2, 2001, p. 209-218.

Research output: Contribution to journalArticle

Rogers, Jason H ; Tsirka, Anna ; Kovacs, Attila ; Blumer, Kendall J. ; Dorn, Gerald W. ; Muslin, Anthony J. / RGS4 reduces contractile dysfunction and hypertrophic gene induction in Gαq overexpressing mice. In: Journal of Molecular and Cellular Cardiology. 2001 ; Vol. 33, No. 2. pp. 209-218.
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