TY - JOUR
T1 - Orientation change of cardiocytes induced by cyclic stretch stimulation
T2 - Time dependency and involvement of protein kinases
AU - Kada, Kenji
AU - Yasui, Kenji
AU - Naruse, Keiji
AU - Kamiya, Kaichiro
AU - Kodama, Itsuo
AU - Toyama, Junji
N1 - Funding Information:
We would like to thank Dr Masahiro Sokabe (Nagoya University School of Medicine) and Dr Philip Palade (The University of Texas Medical Branch) for helpful comments on the manuscript. We also wish to thank Tatsuo Uchida (The University of Texas Medical Branch) for analysing the experimental data statistically. This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture, Japan.
PY - 1999/1
Y1 - 1999/1
N2 - 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.
AB - 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.
KW - Cyclic stretch
KW - Mechanotransduction
KW - Myofibrils
KW - Protein kinase C
KW - Remodeling
KW - Tyrosine kinases
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U2 - 10.1006/jmcc.1998.0865
DO - 10.1006/jmcc.1998.0865
M3 - Article
C2 - 10072732
AN - SCOPUS:0033064916
VL - 31
SP - 247
EP - 259
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 1
ER -