在导致心肌细胞肥大的信号转导途径中对rac1 GTP酶的需求。
A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy.
作者信息
Pracyk J B, Tanaka K, Hegland D D, Kim K S, Sethi R, Rovira I I, Blazina D R, Lee L, Bruder J T, Kovesdi I, Goldshmidt-Clermont P J, Irani K, Finkel T
机构信息
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
出版信息
J Clin Invest. 1998 Sep 1;102(5):929-37. doi: 10.1172/JCI2552.
We have used adenoviral-mediated gene transfer of a constitutively active (V12rac1) and dominant negative (N17rac1) isoform of rac1 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 rac1 is an essential element of the signaling pathway leading to cardiac myocyte hypertrophy.
我们利用腺病毒介导的组成型活性（V12rac1）和显性负性（N17rac1）rac1亚型基因转移，来评估这种小GTP酶在心肌细胞肥大中的作用。新生心肌细胞中V12rac1的表达导致肌节重组和细胞大小增加，这与配体刺激引起的肥大难以区分。此外，V12rac1的表达导致心房利钠肽分泌增加。相比之下，N17rac1而非截短形式的Raf-1的表达，减弱了与去氧肾上腺素刺激相关的形态学肥大。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增加，而N17rac1的表达抑制了去氧肾上腺素诱导的亮氨酸掺入。这些结果表明rac1是导致心肌细胞肥大的信号通路的一个关键要素。
Zotero 插件