The effects of the selective ROCK inhibitor, Y27632, on ET-1-induced hypertrophic response in neonatal rat cardiac myocytes--possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy.
A small GTPase, Rho, participates in agonist-induced cytoskeletal organization and gene expression in many cell types including cardiac myocytes. However, little is known about the functions of Rho's downstream targets in cardiac myocytes. We examined the role of ROCK, a downstream target of Rho, in ET-1-induced hypertrophic response. Y27632, a selective ROCK inhibitor, inhibited ET-1-induced increases in natriuretic peptide production, cell size, protein synthesis, and myofibrillar organization. In addition, a dominant-negative mutant of p160ROCK suppressed ET-1-induced transcription of the BNP gene. These findings suggest that the Rho/ROCK pathway is an important component of ET-1-induced hypertrophic signals in cardiac myocytes.
Kuwahara
K
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Saito
Y
Y
Nakagawa
O
O
Kishimoto
I
I
Harada
M
M
Ogawa
E
E
Miyamoto
Y
Y
Hamanaka
I
I
Kajiyama
N
N
Takahashi
N
N
Izumi
T
T
Kawakami
R
R
Tamura
N
N
Ogawa
Y
Y
Nakao
K
K
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D054460:rho-Associated Kinases
D000577:Amides; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D011994:Recombinant Proteins; D020097:Natriuretic Peptide, Brain; C108830:Y 27632; D009320:Atrial Natriuretic Factor; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020558:GTP Phosphohydrolases