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首页> 外文期刊>Journal of Molecular and Cellular Cardiology >Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch.
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Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch.

机译：慢性压力超负荷下心脏肥大和充血性心力衰竭中的Src和多种MAP激酶激活：与急性机械牵张的比较。

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Activation of members of the mitogen-activated protein (MAP) kinase family and their downstream effectors has been proposed to play a key role in the pathogenesis of cell survival, ischaemic preconditioning, cardiac hypertrophy and heart failure. This study investigated the responses of Src kinase and multiple MAP kinases during the transition from compensated pressure-overload hypertrophy to decompensated congestive heart failure. Extracellular signal-regulated protein kinase (ERK) 1/2, p38, and Src were activated by chronic pressure-overload and their activity was sustained for 8 weeks after aortic banding. In contrast, while p90 ribosomal S6 kinase (90RSK) and big MAP kinase 1 (BMK1) were activated in compensated hypertrophy, their activities were significantly decreased in hearts with heart failure. No changes were found in C-Jun NH2 terminal kinase (JNK) activity after aortic banding. These data suggest that differential activation of MAP kinase family members may contribute to the transition from compensated to decompensated hypertrophy. We also examined acute effects of mechanical stretch on the activation of these kinases in normal and hypertrophied hearts. In the isolated coronary-perfused heart, a balloon in the left ventricle was inflated to achieve minimum end-diastolic pressure of 25 mmHg for 10-20 min. In normal guinea pig hearts, stretch activated ERK1/2, p90RSK, p38, Src, and BMK1 but not JNK. However in hypertrophied hearts, further activation of these kinases was not observed by acute mechanical stretch. Mechanical stretch-induced activation of ERK1/2 and p38 kinase in normal hearts was attenuated significantly by a protein kinase C inhibitor, chelerythrine. We demonstrate that ERK1/2, p90RSK, p38, Src, and BMK1 are activated by chronic pressure-overload and by acute mechanical stretch. These data suggest that Src, BMK1 and p90RSK play a role as novel signal transduction pathways leading to cardiac hypertrophy. In addition, the differential inhibition of p90RSK and BMK1 in hearts with congestive heart failure suggests the specific role of these two kinases to maintain cardiac function under chronic pressure-overload. Copyright 2001 Academic Press.
机译：有人提出，丝裂原活化蛋白（MAP）激酶家族成员及其下游效应子的活化在细胞存活，缺血预处理，心脏肥大和心力衰竭的发病机理中起着关键作用。这项研究调查了Src激酶和多种MAP激酶在从补偿性压力超负荷肥大到失代偿性充血性心力衰竭的过渡过程中的反应。慢性压力超负荷激活细胞外信号调节蛋白激酶（ERK）1/2，p38和Src，主动脉束扎后其活性持续8周。相反，虽然在补偿性肥大中激活了p90核糖体S6激酶（90RSK）和大MAP激酶1（BMK1），但它们在患有心力衰竭的心脏中的活性明显降低。主动脉绑扎后未发现C-Jun NH2末端激酶（JNK）活性发生变化。这些数据表明，MAP激酶家族成员的差异激活可能有助于从代偿性肥大向失代偿性肥大的过渡。我们还检查了正常和肥厚心脏中机械拉伸对这些激酶激活的急性影响。在离体的冠状动脉灌注心脏中，将左心室中的气球充气以达到25 mmHg的最小舒张末期压力10-20分钟。在正常的豚鼠心脏中，拉伸激活的ERK1 / 2，p90RSK，p38，Src和BMK1，而不是JNK。然而，在肥大的心脏中，急性机械牵张未观察到这些激酶的进一步活化。蛋白激酶C抑制剂白屈菜红碱可显着减弱正常人心脏中ERK1 / 2和p38激酶的机械拉伸诱导激活。我们证明ERK1 / 2，p90RSK，p38，Src和BMK1被慢性压力超负荷和急性机械拉伸激活。这些数据表明，Src，BMK1和p90RSK作为导致心脏肥大的新型信号转导途径发挥了作用。此外，在充血性心力衰竭心脏中p90RSK和BMK1的差异抑制表明这两种激酶在慢性压力超负荷下维持心脏功能的特定作用。版权所有2001学术出版社。

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