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首页> 外文期刊>Cellular Signalling >Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes
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Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes

机译：持续暴露于儿茶酚胺会影响成年大鼠心室肌细胞中的cAMP / PKA间隔信号

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In the heart compartmentalisation of cAMP/protein kinase A (PKA) signalling is necessary to achieve a specific functional outcome in response to different hormonal stimuli. Chronic exposure to catecholamines is known to be detrimental to the heart and disrupted compartmentalisation of cAMP signalling has been associated to heart disease. However, in most cases it remains unclear whether altered local cAMP signalling is an adaptive response, a consequence of the disease or whether it contributes to the pathogenetic process. We have previously demonstrated that isoforms of PKA expressed in cardiac myocytes, PKA-I and PKA-II, localise to different subcellular compartments and are selectively activated by spatially confined pools of CAMP, resulting in phosphorylation of distinct downstream targets. Here we investigate cAMP signalling in an in vitro model of hypertrophy in primary adult rat ventricular myocytes. By using a real time imaging approach and targeted reporters we find that that sustained exposure to catecholamines can directly affect cAMP/PKA compartmentalisation. This appears to involve a complex mechanism including both changes in the subcellular localisation of individual phosphodiesterase (PDE) isoforms as well as the relocalisation of PICA isoforms. As a result, the preferential coupling of PICA subsets with different PDEs is altered resulting in a significant difference in the level of cAMP the kinase is exposed to, with potential impact on phosphorylation of downstream targets. (C) 2015 The Authors. Published by Elsevier Inc.
机译：在心脏中，对cAMP /蛋白激酶A（PKA）的信号转导对于实现针对不同激素刺激的特定功能转归是必要的。已知长期暴露于儿茶酚胺会损害心脏，cAMP信号传导的区室化破坏与心脏病有关。然而，在大多数情况下，尚不清楚改变的局部cAMP信号传导是适应性反应，疾病的后果还是它有助于病原过程。我们先前已经证明，在心肌细胞中表达的PKA异构体PKA-I和PKA-II定位于不同的亚细胞区室，并由CAMP的空间受限池选择性激活，从而导致不同的下游靶点磷酸化。在这里，我们调查在成年大鼠心室肌细胞肥大的体外模型中的cAMP信号传导。通过使用实时成像方法和针对性的报道者，我们发现持续暴露于儿茶酚胺会直接影响cAMP / PKA的区室化。这似乎涉及一个复杂的机制，包括单个磷酸二酯酶（PDE）同工型的亚细胞定位的变化以及PICA同工型的重新定位。结果，改变了PICA子集与不同PDE的优先偶联，导致激酶所暴露的cAMP水平显着不同，对下游靶标的磷酸化有潜在影响。 （C）2015作者。由Elsevier Inc.发布

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