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 language | English (US) |
|---|---|
| Pages (from-to) | 209-218 |
| Number of pages | 10 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 33 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2001 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - RGS4 reduces contractile dysfunction and hypertrophic gene induction in Gαq overexpressing mice
AU - Rogers, Jason H
AU - Tsirka, Anna
AU - Kovacs, Attila
AU - Blumer, Kendall J.
AU - Dorn, Gerald W.
AU - Muslin, Anthony J.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Cardiac hypertrophy
KW - G protein
KW - RGS
KW - Signal transduction
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=0034967283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034967283&partnerID=8YFLogxK
U2 - 10.1006/jmcc.2000.1307
DO - 10.1006/jmcc.2000.1307
M3 - Article
C2 - 11162127
AN - SCOPUS:0034967283
VL - 33
SP - 209
EP - 218
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 2
ER -