Cdc42 plays a critical role in assembly of sarcomere units in series of cardiac myocytes.
Cardiomyocyte hypertrophy is observed in various cardiovascular diseases and causes heart failure. We here examined the role of small GTP-binding proteins of Rho family in phenylephrine (PE)-or leukocyte inhibitory factor (LIF)-induced hypertrophic morphogenesis of cultured neonatal rat cardiomyocytes. Both LIF and PE increased cell size of cardiomyocytes. LIF induced an increase in the length/width ratio of cardiomyocytes, while PE did not change the ratio. Adenoviral gene transfer of constitutively active mutants of Cdc42 increased the length/width ratio of cardiomyocytes and dominant negative mutants of Cdc42 conversely inhibited LIF-induced cell-elongation, while mutants of RhoA and Rac1 did not affect the length/width ratio of cardiomyocytes. These results suggest that Cdc42, but not RhoA and Rac1, is involved in LIF-induced sarcomere assembly in series in cardiomyocytes.
Nagai
Toshio
T
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Tanaka-Ishikawa
Mariko
M
Aikawa
Ryuichi
R
Ishihara
Hisamitsu
H
Zhu
Weidung
W
Yazaki
Yoshio
Y
Nagai
Ryozo
R
Komuro
Issei
I
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D005822:Genetic Vectors; D008222:Lymphokines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000648:ultrastructure*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology
D008222:Lymphokines; C010598:leukocyte inhibitory factor; D010656:Phenylephrine; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein