RGS4 Reduces Contractile Dysfunction and Hypertrophic Gene Induction in Gα qOverexpressing Mice
Journal of molecular and cellular cardiology, 2001•Elsevier
The intrinsic GTPase activity of Gα qis 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 Gα qin myocardium exhibit cardiac
hypertrophy, enhanced PKCξ membrane translocation, embryonic gene expression, and
depressed cardiac contractility. We recently reported that transgenic mice with cardiac-
specific expression of RGS4, a Gα qand Gα iGTPase activator, exhibit decreased left …
expressed in the heart; however, their functional relevance in vivo is unknown. Transgenic
mice with cardiac-specific overexpression of Gα qin myocardium exhibit cardiac
hypertrophy, enhanced PKCξ membrane translocation, embryonic gene expression, and
depressed cardiac contractility. We recently reported that transgenic mice with cardiac-
specific expression of RGS4, a Gα qand Gα iGTPase activator, exhibit decreased left …
The intrinsic GTPase activity of Gα qis 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 Gα qin myocardium exhibit cardiac hypertrophy, enhanced PKCξ membrane translocation, embryonic gene expression, and depressed cardiac contractility. We recently reported that transgenic mice with cardiac-specific expression of RGS4, a Gα qand Gα iGTPase activator, exhibit decreased left ventricular hypertrophy and ANF induction in response to pressure overload. To test the hypothesis that RGS4 can act as a Gα q-specific GTPase activating protein (GAP) in the in vivo heart, dual transgenic Gα q-40xRGS4 mice were generated to determine if RGS4 co-expression would ameliorate the Gα q-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. PKC ξ 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 Gα qin the in vivo heart, and demonstrate that its regulated expression can have pathophysiologic consequences.
Elsevier