Pressure overload selectively up-regulates Ca2+/Calmodulin-dependent protein kinase II in vivo
Pressure overload selectively up-regulates Ca2+/Calmodulin-dependent protein kinase II in vivo
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DOI：
10.1210/me.2002-0350
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发表时间：
2003-02-01
影响因子：
--
通讯作者：
Means, AR
中科院分区：
文献类型：
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作者：
Colomer, JM;Mao, L;Means, AR
多功能钙/钙调蛋白依赖性蛋白激酶 (CaMK) 转导的信号被认为可以调节肥大的发展。我们利用横主动脉缩窄 (TAC) 诱导小鼠心脏肥大，探讨了三种多功能 CaMK I、II 和 IV 在此过程中的作用。我们发现 TAC 后 7 天总 CaMK 活性增加了 33%。然而，在心室中表达的 CaMIKI 或在心室中检测不到的 CaMKIV 水平没有变化。此外，CaMKIV 基因缺失的小鼠会出现心室肥大，并诱导选定的肥大标志物 mRNA 的表达，表明在肥大发展过程中的任何时间都不需要 CaMKIV。另一方面，TAC 确实增加了源自 γ 和 δ 基因的 CaMKII 特定亚型的 mRNA 和蛋白质水平。这些亚型包括定位于细胞质和细胞核的亚型。总的来说，CaMKII 亚型水平的增加导致心室中 CaMKII 的 Ca2+/钙调蛋白独立活性的持续增加。我们得出结论，CaMKII 是最有可能介导 Ca2+ 依赖性蛋白磷酸化事件以响应 TAC 诱导的心脏肥大的多功能 CaMK。
Signals transduced by the multifunctional calcium/calmodulin-dependent protein kinases (CaMKs), have been suggested to regulate the development of hypertrophy. We address the role of the three multifunctional CaMKs, CaMK I, II, and IV, in this process using transverse aortic constriction (TAC) to induce cardiac hypertrophy in mice. We find a 33% increase in total CaMK activity 7 d after TAC. However, there are no changes in the levels of CaMIKI, which is expressed in the ventricles, or CaMKIV, which is not detectable in the ventricles. Moreover, mice null for the CaMKIV gene develop ventricular hypertrophy and induce the expression of selected hypertrophy marker mRNAs, indicating that CaMKIV is not required at any time during the development of hypertrophy. On the other hand, TAC does increase both mRNA and protein levels of specific isoforms of CaMKII derived from both gamma and delta genes. Included among these isoforms are those that localize to both cytoplasm and nucleus. Collectively, the increased levels of CaMKII isoforms result in a constitutive increase in the Ca2+/calmodulin-independent activity of CaMKII in the ventricles. We conclude that CaMKII is the multifunctional CaMK most likely to mediate Ca2+-dependent protein phosphorylation events in response to TAC-induced cardiac hypertrophy.