Orientation change of cardiocytes induced by cyclic stretch stimulation

Time dependency and involvement of protein kinases

Kenji Kada, Kenji Yasui, Keiji Naruse, Kaichiro Kamiya, Itsuo Kodama, Junji Toyama

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Mechanical stress has been implicated as one of the growth regulators in the heart. We investigated the effect of cyclic stretch stimulation on morphology and orientation of cultured cardiocytes. Embryonic rat (17 days postcoital) cardiomyocytes cultured on silicone dishes were cyclically stretched to 120% in length at a frequency of 30 cycles/min. After 12 h, in the initial stage of cultivation, cardiocytes and intracellular myofibrils oriented parallel to the stretch direction. When the stretch stimulus was prolonged to 24-48 h, myofibrils that oriented perpendicular to the stretch direction emerged. Furthermore, when the cells were stretched only in the later stage (after 24 h of cultivation), both cells and myofibrils tended to orient perpendicular to the stretch direction. Next we examined the effects of chemical compounds on these phase-related changes in myofibril orientation. None of the drugs tested (H-7, HA-1004, staurosporine, herbimycin A, genistein, GdCl3, and EGTA) blocked the parallel orientation of myofibrils induced by the initial-stage stretch. By contrast, H-7, staurosporine, herbimycin A, and genistein did inhibit almost completely the perpendicular orientation of the myofibrils induced by the late-stage stretch, but HA-1004, GdC13, or EGTA did not. Immunoblotting study using anti-phsophotyrosine antibody indicated that tyrosine phosphorylation of a protein of about 125 kDa was enhanced in a time-dependent manner by the late-stage stretch, but not by the initial-stage stretch. In conclusion: the alignment change induced by cyclic stretch depends on the stage of cultivation: with stretch in the initial stage (within 12 h), cells and myofibrils orient parallel to the stretch: with stretch in the later stage (after 24 h), they orient perpendicular to the stretch. The effect of stretch in the later stage is likely mediated by protein kinase C and tyrosine kinase pathways.

Original languageEnglish
Pages (from-to)247-259
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 1999
Externally publishedYes

Fingerprint

Myofibrils
Protein Kinases
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Staurosporine
Genistein
Egtazic Acid
Mechanical Stress
Silicones
Immunoblotting
Cardiac Myocytes
Protein-Tyrosine Kinases
Tyrosine
Anti-Idiotypic Antibodies
Phosphorylation
Growth
Pharmaceutical Preparations
Direction compound
Proteins

Keywords

  • Cyclic stretch
  • Mechanotransduction
  • Myofibrils
  • Protein kinase C
  • Remodeling
  • Tyrosine kinases

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Orientation change of cardiocytes induced by cyclic stretch stimulation : Time dependency and involvement of protein kinases. / Kada, Kenji; Yasui, Kenji; Naruse, Keiji; Kamiya, Kaichiro; Kodama, Itsuo; Toyama, Junji.

In: Journal of Molecular and Cellular Cardiology, Vol. 31, No. 1, 01.1999, p. 247-259.

Research output: Contribution to journalArticle

Kada, Kenji ; Yasui, Kenji ; Naruse, Keiji ; Kamiya, Kaichiro ; Kodama, Itsuo ; Toyama, Junji. / Orientation change of cardiocytes induced by cyclic stretch stimulation : Time dependency and involvement of protein kinases. In: Journal of Molecular and Cellular Cardiology. 1999 ; Vol. 31, No. 1. pp. 247-259.
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