Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload
Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload
复制标题
抑制糖原合酶激酶3对急性压力超负荷时心肌肥厚的影响
DOI：
10.1007/s11748-009-0562-6
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发表时间：
2010
影响因子：
1.2
通讯作者：
Hiroshi Yamamoto
中科院分区：
文献类型：
--
作者：
F. Yamamoto;Hiroshi Yamamoto
心肌肥大已被认为是对各种外部刺激的适应性反应（例如，心肌梗死、压力超负荷、儿茶酚胺治疗、内分泌紊乱），其涉及介导从外部刺激到核蛋白合成的信号通路的几种亚细胞因子。糖原合成酶激酶-3 β（Glycogen synthase kinase-3 β，GSK-3β）是调节核转录因子如活化T细胞（activated T-cell，NFAT）蛋白的亚细胞因子之一，与心肌肥大过程中的基因编程有关。另一方面，已知GSK-3β在心脏发生的Wnt信号传导中是心肌细胞生长的调节剂，其参与β-连环蛋白降解。据报道，GSK-3β的抑制可诱导心脏肥大。Tateishi等人在使用6周龄Wister大鼠的主动脉缩窄诱导的急性肥大模型中证明，如果GSK-3b被LiCl抑制，则观察到β-连环蛋白表达上调和额外的肥大。他们认为Li 2+通过GSK-3β-β-catenin途径对压力超负荷诱导的肥大具有累加效应。他们的文章提供了关于急性压力超负荷时肥大肌细胞生长机制的有希望的信息。
Myocardial hypertrophy has been recognized to be an adaptive response to a variety of external stimuli (e.g., myocardial infarction, pressure overload, catecholamine treatment, endocrine disorders) that are involved in several subcellular factors that mediate signaling pathways, from external stimuli to nuclear protein synthesis. Glycogen synthase kinase-3β (GSK-3β) is one of the subcellular factors that regulate nuclear transcription factors, such as activated T-cell (NFAT) proteins, that are related to gene programming during cardiac hypertrophy. On the other hand, GSK-3β, known as a regulator of cardiomyocyte growth in Wnt signaling of cardiogenesis, is involved in β-catenin degradation. Inhibition of GSK-3β has been reported to induce cardiac hypertrophy. Tateishi et al. demonstrated in an aortic constriction-induced acute hypertrophy model using 6-week-old Wister rats that if GSK-3b is inhibited by LiCl up-regulated β-catenin expression and additional hypertrophy were observed. They suggested that Li2+had an additive effect on pressure overload-induced hypertrophy through the GSK-3β—β-catenin pathway. Their article provides promising information on the mechanism of hypertrophic myocyte growth during acute pressure overload.