Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy.
Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy.
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Epac 基因表达的发育变化及其在心肌肥大中的上调。
DOI：
10.1152/ajpheart.00159.2007
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Ishikawa,Yoshihiro
中科院分区：
文献类型：
--
作者：
Ulucan,Coskun;Wang,Xu;Baljinnyam,Erdene;Bai,Yunzhe;Okumura,Satoshi;Sato,Motohiko;Minamisawa,Susumu;Hirotani,Shinichi;Ishikawa,Yoshihiro
尽管已表明 Epac1 mRNA 普遍表达，Epac2 mRNA 主要在脑和内分泌组织中表达，但这些分子的发育和病理生理变化尚未得到表征。通过 RT-PCR 分析对小鼠心脏、大脑、肾脏和肺的发育变化进行了分析，结果显示 Epac2 mRNA 的发育变化比 Epac1 更为剧烈。只有肾脏中的 Epac2 mRNA 显示出短暂的表达模式，并在成年后急剧下降。除了发育变化之外，我们还发现，在慢性异丙肾上腺素输注或横主动脉带造成的压力超负荷引起的心肌肥大中，Epac 基因表达上调。 Epac1 和 Epac2 mRNA 在异丙肾上腺素诱导的左心室肥厚中均上调，而在压力超负荷诱导的左心室肥厚中仅 Epac1 升高。用胎牛血清刺激心肌成肌细胞H9c2，可诱导心肌细胞肥大，上调Epac1蛋白表达。我们还证明，就化学计量而言，Epac 相对于 Rap 是 Epac-Rap 信号通路中的限制部分，并且 Epac 刺激导致 ERK1/2 的激活。我们的数据表明 Epac 在器官发生以及生理和病理生理过程（例如心脏肥大）中发挥功能作用。此外，我们的结果表明 Epac 的化学计量比 Rap 在细胞生物效应中的重要性。
Although it has been shown that Epac1 mRNA is expressed ubiquitously and Epac2 mRNA predominantly in the brain and endocrine tissues, developmental and pathophysiological changes of these molecules have not been characterized. Developmental changes were analyzed in murine heart, brain, kidneys, and lungs by RT-PCR analysis, which revealed more drastic developmental changes of Epac2 mRNA than Epac1. Only the Epac2 mRNA in kidney showed a transient expression pattern with dramatic decline into adulthood. In addition to developmental changes, we found that Epac gene expression was upregulated in myocardial hypertrophy induced by chronic isoproterenol infusion or pressure overload by transverse aortic banding. Both Epac1 and Epac2 mRNA were upregulated in isoproterenol-induced left ventricular hypertrophy, whereas only Epac1 was increased in pressure overload-induced hypertrophy. Stimulation of H9c2, cardiac myoblast cells, with fetal calf serum, which can induce myocyte hypertrophy, upregulated Epac1 protein expression. We also demonstrated that Epac was the limiting moiety, relative to Rap, in the Epac-Rap signaling pathway in terms of stoichiometry and that Epac stimulation led to the activation of ERK1/2. Our data suggest the functional involvement of Epac in organogenesis and also in physiological as well as pathophysiological processes, such as cardiac hypertrophy. Furthermore, our results suggest the importance of the stoichiometry of Epac over that of Rap in cellular biological effects.
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56.9
作者：
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影响因子：
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DOI：
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发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
Biochem Biophys Res Commun 334
影响因子：
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作者：
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