A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy
A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy
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DOI：
10.1172/jci2552
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发表时间：
1998-09-01
影响因子：
15.9
通讯作者：
Finkel, T
中科院分区：
文献类型：
--
作者：
Pracyk, JB;Tanaka, K;Finkel, T
我们使用腺病毒介导的基因转移的成分活性(V12rac1)和显性阴性(N17rac1)的RAD亚型来评估这种小的GTP酶在心肌细胞肥大中的作用。V12rac1在新生儿心肌细胞中的表达导致肌瘤重组和细胞大小增加，这与配体刺激的肥大没有区别。此外，V12rac1的表达还导致心钠素分泌增加。相反，N17rac1的表达，而不是Raf-1的截断形式，减轻了与苯肾上腺素刺激相关的形态肥大。与观察到的对形态的影响一致，V12rac1的表达导致新蛋白质合成的增加，而N17rac1的表达抑制了苯肾上腺素诱导的亮氨酸掺入。这些结果表明，RAD是导致心肌细胞肥大的信号通路中的一个重要元件。
We have used adenoviral-mediated gene transfer of a constitutively active (V12rac1) and dominant negative (N17rac1) isoform of rad to assess the role of this small GTPase in cardiac myocyte hypertrophy. Expression of V12rac1 in neonatal cardiac myocytes results in sarcomeric reorganization and an increase in cell size that is indistinguishable from ligand-stimulated hypertrophy. In addition, V12rac1 expression leads to an increase in atrial natriuretic peptide secretion. In contrast, expression of N17rac1, but not a truncated form of Raf-1, attenuated the morphological hypertrophy associated with phenylephrine stimulation. Consistent with the observed effects on morphology, expression of V12rac1 resulted in an increase in new protein synthesis, while N17rac1 expression inhibited phenylephrine-induced leucine incorporation. These results suggest rad is an essential element of the signaling pathway leading to cardiac myocyte hypertrophy.