Uniaxial stretch-induced regulation of mitogen-activated protein kinase, Akt and p70 S6 kinase in the ageing Fischer 344 x Brown Norway rat aorta.
Uniaxial stretch-induced regulation of mitogen-activated protein kinase, Akt and p70 S6 kinase in the ageing Fischer 344 x Brown Norway rat aorta.
复制标题
衰老 Fischer 344 x Brown 挪威大鼠主动脉中丝裂原激活蛋白激酶、Akt 和 p70 S6 激酶的单轴拉伸诱导调节。
DOI：
10.1113/expphysiol.2007.037275
复制
发表时间：
2007
影响因子：
2.7
通讯作者：
Blough,EricR
中科院分区：
文献类型：
--
作者：
Rice,KevinM;Desai,DevashishH;Preston,DeborahL;Wehner,PauletteS;Blough,EricR
衰老对心血管系统的影响导致细胞形态和功能的实质性变化。调控这些变化的变量尚不清楚；然而，有一组信号分子可能在调节众多细胞反应(包括控制细胞生长、分化和适应)中具有特别重要的作用，它们是与丝裂原活化蛋白激酶(MAPK)信号系统相关的蛋白质。MAPK与p70 S6K信号级联一起，已经成为调节许多与机械转导相关的细胞反应的关键组件。在本研究中，我们观察了单轴拉伸对成年(6月龄)、老年(30月龄)和超龄(36月龄)Fischer 344/NNiaHSd×Brown挪威/Binia(FBN)大鼠MAPK和p70 S6K通路的激活能力。Western blotting检测MAPK家族蛋白细胞外信号调节激酶(Erk)1/2、p38-和c-jun NH2-末端激酶(JNK)-MAPKs的表达和活性随年龄的增加而不同。使用AneX活体主动脉准备材料的急性单轴拉伸20%的15min间隔显示出类似的ERK1/2、p38-和JNK-MAPK的调节。然而，衰老改变了单轴诱导的p70S6K通路信号。这些观察结果证实了先前的数据，表明MAPK蛋白是受机械调节的，也表明p70S6K信号的表达和激活随着年龄的增长而受到不同的控制。综上所述，这些数据可能有助于部分解释与年龄相关的血管形态、功能和损伤反应的变化。
The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen‐activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction‐related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult (6‐month‐old), aged (30‐month‐old) and very aged (36‐month‐old) Fischer 344/NNiaHSd × Brown Norway/BiNia (FBN) rats. Western blotting of the MAPK family proteins extracellular signal‐regulated kinase (Erk) 1/2, p38‐ and c‐Jun NH2‐terminal kinase (Jnk)‐MAPKs showed differential expression and activation between these proteins with age. An acute 15 min interval of 20% uniaxial stretch using anex vivoaortic preparation demonstrated similar regulation of Erk1/2, p38‐ and Jnk‐MAPK. However, ageing altered uniaxial induced p70 S6k pathway signalling. These observations confirm previous data demonstrating that MAPK proteins are mechanically regulated and also suggest that p70 S6k signalling expression and activation are controlled differently with ageing. Taken together, these data may help to explain, in part, the age‐related changes in vascular morphology, function and response to injury.