caa a22 4500 477120741 CHVBK 20180405111636.0 cr unu---uuuuu 170330e19960301xx s 000 0 eng 10.1007/BF00408658 doi (NATIONALLICENCE)springer-10.1007/BF00408658 Molecular aspects of mechanical stress-induced cardiac hypertrophy [Elektronische Daten] [Tsutomu Yamazaki, Issei Komuro, Yoshio Yazaki] To elucidate the signal transduction pathway from external stimuli to nuclear gene expression in mechanical stress-induced cardiac hypertrophy, we examined the time course of activation of protein kinases such as Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK), MAP kinases (MAPKs) and 90-kDa ribosomal S6 kinase (p90rsk) in neonatal rat cardiomyocytes. Mechanical stretch rapidly activated Raf-1 and its maximal activation was observed at 1-2 min after stretch. The activity of MAPKK was also increased by stretch, with a peak at 5 min after stretch. In addition, MAPKs and p90rsk were maximally activated at 8 min and at 10-30 min after stretch, respectively. Next, the relationship between mechanical stress-induced hypertrophy and the cardiac renin-angiotensin system was investigated. When the stretch-conditioned culture medium was transferred to the culture dish of non-stretched cardiac myocytes, the medium activated MAPK activity slightly but significantly, and the activation was completely blocked by the type 1 angiotensin II receptor antagonist, CV-11974. However, activation of Raf-1 and MAPKs provoked by stretching cardiomyocytes was only partially suppressed by pretreatment with CV-11974. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1, MAPKK, MAPKs and p90rsk, and that angiotensin II, which is secreted from stretched myocytes, activates a part of these protein kinases. Kluwer Academic Publishers, 1996 signal transduction nationallicence Raf-1 kinase nationallicence MAP kinase kinase nationallicence MAP kinase nationallicence S6 kinase nationallicence angiotensin II nationallicence MAPK : mitogen-activated protein kinase nationallicence MAPKK : MAP kinase kinase nationallicence Raf-1 - Raf- 1 kinase : p90rsk, 90 kDa ribosomal S6 kinase nationallicence AngII - angiotensin II nationallicence MAPKKK : MAP kinase kinase kinase nationallicence rMAPK : recombinant MAPKK fused to gluthathione S transferase nationallicence MMAKK : recombinant MAPK fused to maltose binding protein nationallicence MBP : myelin basic protein nationallicence ACE : angiotensin-converting enzyme nationallicence Yamazaki Tsutomu Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan aut Komuro Issei Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan aut Yazaki Yoshio Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan aut Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 163-164/1(1996-03-01), 197-201 0300-8177 163-164:1<197 1996 163-164 11010 https://doi.org/10.1007/BF00408658 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00408658 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamazaki Tsutomu Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan aut NATIONALLICENCE 700 1- Komuro Issei Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan aut NATIONALLICENCE 700 1- Yazaki Yoshio Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 163-164/1(1996-03-01), 197-201 0300-8177 163-164:1<197 1996 163-164 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer