Activation of the ERK1/2 pathway by the CaMEK gene via adeno-associated virus serotype 9 in cardiomyocytes
Activation of the ERK1/2 pathway by the CaMEK gene via adeno-associated virus serotype 9 in cardiomyocytes
复制标题
CaMEK 基因通过腺相关病毒血清型 9 在心肌细胞中激活 ERK1/2 通路
DOI：
10.4238/2012.october.17.1
复制
发表时间：
2012-01-01
影响因子：
0.4
通讯作者：
Liu, F.
中科院分区：
文献类型：
--
作者：
Yang, Y. -N.;Ji, W. -N.;Liu, F.
细胞外信号调节激酶（ERK1/2）是丝裂原激活蛋白激酶之一，是再灌注损伤挽救激酶通路的关键组成部分，在保护心肌免受致命性缺血再灌注损伤中发挥着重要作用。丝裂原激活蛋白激酶激酶 1 (CaMEK) 的组成性激活可促进 ERK1/2 表达，从而有望对心脏缺血再灌注损伤发挥保护作用。腺相关病毒血清型 9 载体 (AVV9) 因其转导非分裂细胞的非致病性能力及其长期转基因表达而成为针对人类疾病的基因治疗的新工具。我们使用重组AAV9载体将CaMEK基因导入心肌细胞，并评估AAV9载体介导的CaMEK基因转染是否可以增强ERK1/2的长期表达和活性。我们的观察结果表明，AAV9 介导的基因表达优先限于心肌细胞，并且介导的 CaMEK 基因转染增强了 ERK1/2 磷酸化的表达，从而上调了 ERK1/2 下游组件及其转录因子的表达。
Extracellular signal-regulated kinase (ERK1/2) is one of the mitogen-activated protein kinases, key components of the reperfusion injury salvage kinase pathway, which plays an important role in protecting the myocardium from lethal ischemia-reperfusion injury. Constitutive activation of the mitogen-activated protein kinase kinase 1 (CaMEK) can promote ERK1/2 expression, which is thereby expected to exert protective action on the heart against ischemia-reperfusion injury. The adeno-associated virus serotype 9 vector (AVV9) is a novel tool for gene therapies targeting human diseases owing to its nonpathogenic capability for transducing nondividing cells and its long-term transgene expression. We used a recombinant AAV9 vector to deliver the CaMEK gene into cardiomyocytes and assessed whether AAV9 vector-mediated CaMEK gene transfection could enhance the long-term expression and activity of ERK1/2. Our observations suggest that AAV9-mediated gene expression is preferentially restricted to cardiomyocytes and that mediated CaMEK gene transfection enhanced the expression of ERK1/2 phosphorylation and consequently upregulated the expression of downstream components of ERK1/2 and its transcription factors.