Endothelin-1 up-regulates p115RhoGEF in embryonic rat cardiomyocytes during the hypertrophic response.
In cardiomyocytes, certain extracellular stimuli that activate heterotrimeric G protein-coupled receptors (GPCRs) can induce hypertrophy by regulating gene expression and increasing protein synthesis. We investigated if rat embryonic cardiomyocytes (H9c2) underwent variations in the expression levels and subcellular distribution of key components of GPCR-activated signaling pathways during endothelin-1 (ET-1)-induced hypertrophic response. A significant increase of p115RhoGEF protein level was evident in ET-1-treated cells. Real-time quantitative PCR showed RhoGEF mRNA levels were significantly increased. Inhibition of the Rho-associated kinase (ROCK) caused a significant decrease of p115RhoGEF protein in the nuclear fraction, whereas an inhibitor of PKC induced a redistribution of the protein between membrane/organelle and nuclear fractions. The ROCK inhibitor also decreased H9c2 cell hypertrophic response. These results indicate that ROCK and its downstream target molecules, which are involved in inducing the hypertrophic response, are also implicated in signaling the up-regulation of the p115RhoGEF protein.
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy.
Francesca
F
Porchia
Mara
M
Papucci
Claudia
C
Gargini
Antonella
A
Asta
Giuseppina
G
De Marco
Patrizia
P
Agretti
Massimo
M
Tonacchera
Maria Rosa
MR
Mazzoni
D000818:Animals; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology*; D019332:Endothelin-1 / Q000494:pharmacology*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006984:Hypertrophy; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D019332:Endothelin-1; D020662:Guanine Nucleotide Exchange Factors; D021122:Protein Subunits; D064067:Rho Guanine Nucleotide Exchange Factors; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein