Yamazaki T, Yazaki Y
Health Service Center, University of Tokyo.
Nihon Rinsho. 1997 Aug;55(8):1988-93.
We examined the signal transduction pathway for the development of cardiac hypertrophy induced by high blood pressure. The activities of Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK), MAP kinases (MAPKs) and 90-kDa ribosomal S6 kinase (p90rsk) was examined by passively stretching neonatal rat cardiomyocytes in vitro. Mechanical stretch activated these protein kinases transiently and sequentially: the maximal activation of Raf-1, MAPKK, MAPKs and p90rsk was observed at 2 minutes, 5 minutes, 8 minutes and 10 approximately 30 minutes, respectively. Both angiotensin II (AngII) and endothelin-1 (ET-1) were constitutively secreted from cultured cardiomyocytes, and a significant increase in the concentration was recognized in the culture medium of cardiomyocytes within 10 minutes after stretch. ET-1 mRNA levels were also increased in cardiomyocytes at 30 minutes after stretch. Moreover, ET-1 and AngII synergistically activated Raf-1 and MAPKs in cultured cardiomyocytes. In conclusion, mechanical stretch stimulates secretion and production of AngII and ET-1 in cultured cardiomyocytes, and both vasoconstrictive peptides may play an important role in mechanical stress (high blood pressure)-induced cardiac hypertrophy.
我们研究了高血压诱导心脏肥大发展的信号转导途径。通过体外被动拉伸新生大鼠心肌细胞，检测了Raf-1激酶（Raf-1）、丝裂原活化蛋白激酶激酶（MAPKK）、丝裂原活化蛋白激酶（MAPKs）和90-kDa核糖体S6激酶（p90rsk）的活性。机械拉伸可瞬时且依次激活这些蛋白激酶：Raf-1、MAPKK、MAPKs和p90rsk的最大激活分别在约2分钟、5分钟、8分钟和10至30分钟时观察到。血管紧张素II（AngII）和内皮素-1（ET-1）均由培养的心肌细胞组成性分泌，拉伸后10分钟内心肌细胞培养基中的浓度显著升高。拉伸后30分钟心肌细胞中ET-1 mRNA水平也升高。此外，ET-1和AngII在培养的心肌细胞中协同激活Raf-1和MAPKs。总之，机械拉伸刺激培养的心肌细胞中AngII和ET-1的分泌和产生，这两种血管收缩肽可能在机械应激（高血压）诱导的心脏肥大中起重要作用。
