Gα13 stimulates gene expression and increases cell size in cultured neonatal rat ventricular myocytes

Abstract

Objectives: Constitutively-active Gα₁₃ causes permissive cell types to proliferate or undergo phenotypic transformation implying a role for G₁₃ in the control of cell growth. Cardiac myocytes are terminally-differentiated cells which respond to growth stimuli by increasing in size rather than by cell division. The objective of this study was to determine whether constitutively-active Gα₁₃ is able to induce a hypertrophic phenotype in cardiac myocytes. Methods: Cultured neonatal rat ventricular myocytes were transiently transfected with an expression vector (pRC/RSV) encoding wild-type Gα₁₃ or constitutively-active Gα₁₃Q226L. Effects on transcription were monitored by co-transfected luciferase (LUX) reporter genes under the control of promoters responsive to hypertrophic stimuli. Cell size was determined by planimetry. Results: Transfection of neonatal myocytes with Gα₁₃Q226L, but not wild-type Gα₁₃, stimulated ANF638LUX and ANF3003LUX expression to 3.0±0.3- and 4.3±0.6-fold of the control, respectively. Likewise, Gα₁₃Q226L stimulated vMLC250LUX and vMLC2700LUX expression to 3.9±1.0- and to 7.7±1.7-fold of controls, respectively, but there was relatively little effect of Gα₁₃Q226L on c-fos-SRE- and β-MHC promoter activity. The effects of Gα₁₃Q226L on ANF3003LUX were inhibited by expression of C3 exoenzyme. Wild-type Gα₁₃ and Gα₁₃Q226L increased myocyte area from 869±43 μm² in control transfections to 1287±64 μm² and 1278±59 μm², respectively. Conclusion: We conclude that Gα₁₃Q226L is able to induce gene expression and morphological changes associated with a hypertrophic response in cardiac myocytes and that the transcriptional effects may be mediated through a Rho-dependent mechanism.