TY - JOUR
T1 - Pulsatile stretch activates mitogen-activated protein kinase (MAPK) family members and focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes
AU - Seko, Yoshinori
AU - Seko, Yuko
AU - Takahashi, Naoyuki
AU - Tobe, Kazuyuki
AU - Kadowaki, Takashi
AU - Yazaki, Yoshio
N1 - Funding Information:
This work was supported by a grant for cardiomyopathy from the Ministry of Health and Welfare, Japan, a grant for scientific research from the Ministry of Education, Science and Culture, Japan, a grant from Sankyo Foundation of Life Science, Japan Heart Foundation/ Pfizer Pharmaceuticals Grant for Research on Coronary Artery Disease, and a grant from Study Group of Molecular Cardiology. We thank Dr. Hisataka Sabe (Department of Molecular Biology, Osaka BioScience Institute, Osaka, Japan) for anti-p125FAK polyclonal antibody. We also thank Kaori Takahashi for excellent technical assistance.
PY - 1999/5/27
Y1 - 1999/5/27
N2 - Recently, we demonstrated that pulsatile mechanical stretch induced rapid secretion of vascular endothelial growth factor (VEGF) by cultured rat cardiac myocytes in vitro. To investigate whether pulsatile stretch activates intracellular signaling in cardiac myocytes, we examined the activation of mitogen-activated protein kinase (MAPK) family members and focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes. We found that pulsatile stretch rapidly phosphorylated p44/p42 MAPKs (extracellular signal-regulated protein kinase [ERK] 1/2), stress-activated protein kinase (SAPK), p38MAPK, and p125(FAK). The stretch-induced activation of ERKs was at least partly mediated by VEGF, which was shown to be induced by transforming growth factor (TGF)-β, and was also partly dependent on tyrosine kinases as well as protein kinase C (PKC). These data provide the direct evidence that pulsatile stretch can activate intracellular signaling in cardiac myocytes and that this was at least partly mediated by VEGF, which may play a role in cardiac adaptation to mechanical overload.
AB - Recently, we demonstrated that pulsatile mechanical stretch induced rapid secretion of vascular endothelial growth factor (VEGF) by cultured rat cardiac myocytes in vitro. To investigate whether pulsatile stretch activates intracellular signaling in cardiac myocytes, we examined the activation of mitogen-activated protein kinase (MAPK) family members and focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes. We found that pulsatile stretch rapidly phosphorylated p44/p42 MAPKs (extracellular signal-regulated protein kinase [ERK] 1/2), stress-activated protein kinase (SAPK), p38MAPK, and p125(FAK). The stretch-induced activation of ERKs was at least partly mediated by VEGF, which was shown to be induced by transforming growth factor (TGF)-β, and was also partly dependent on tyrosine kinases as well as protein kinase C (PKC). These data provide the direct evidence that pulsatile stretch can activate intracellular signaling in cardiac myocytes and that this was at least partly mediated by VEGF, which may play a role in cardiac adaptation to mechanical overload.
UR - http://www.scopus.com/inward/record.url?scp=0033609354&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1999.0720
DO - 10.1006/bbrc.1999.0720
M3 - 学術論文
C2 - 10334907
AN - SCOPUS:0033609354
SN - 0006-291X
VL - 259
SP - 8
EP - 14
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -