title: G alpha 13 stimulates gene expression and increases cell size in cultured neonatal rat ventricular myocytes.
abstract: OBJECTIVE
  Constitutively-active G alpha 13 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 G alpha 13 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 G alpha 13 or constitutively-active G alpha 13Q226L. 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 G alpha 13Q226L, but not wild-type G alpha 13, stimulated ANF638LUX and ANF3003LUX expression to 3.0 +/- 0.3- and 4.3 +/- 0.6-fold of the control, respectively. Likewise, G alpha 13Q226L 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 G alpha 13Q226L on c-fos-SRE- and beta-MHC promoter activity. The effects of G alpha 13Q226L on ANF3003LUX were inhibited by expression of C3 exoenzyme. Wild-type G alpha 13 and G alpha 13Q226L increased myocyte area from 869 +/- 43 micron 2 in control tranfections to 1287 +/- 64 micron 2 and 1278 +/- 59 microns, respectively.
  
  
  CONCLUSIONS
  We conclude that G alpha 13Q226L 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.
authors.affiliation: NHL1 Division, Imperial College School of Medicine, London, UK. stephen.fuller@ic.ac.uk
authors.forename: S G
authors.initials: SG
authors.lastname: Finn
authors.forename: S G
authors.initials: SG
authors.lastname: Plonk
authors.forename: S J
authors.initials: SJ
authors.lastname: Fuller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D008156:Luciferases; D019204:GTP-Binding Proteins