title: Cdc42 plays a critical role in assembly of sarcomere units in series of cardiac myocytes.
abstract: 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.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nagai
authors.forename: Mariko
authors.initials: M
authors.lastname: Tanaka-Ishikawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Aikawa
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
authors.forename: Weidung
authors.initials: W
authors.lastname: Zhu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yazaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: 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
chemical_list: D008222:Lymphokines; C010598:leukocyte inhibitory factor; D010656:Phenylephrine; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein