Katanosaka Yuki, Kim Bongju, Wakabayashi Shigeo, Matsuoka Satoshi, Shigekawa Munekazu
Department of Molecular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
Ann N Y Acad Sci. 2007 Mar;1099:373-6. doi: 10.1196/annals.1387.024.
Both protein kinase Calpha-dependent Na+/Ca2+ exchanger1 (NCX1) phosphorylation and calcineurin activity are required for the depression of NCX activity observed in chronically phenylephrine (PE)-treated hypertrophic neonatal rat cardiomyocytes. In this study, we explored the possibility that the same changes occur in vivo hypertrophy. In the hypertrophic hearts of thoracic aortic-banded (TAB) mice, NCX1 phosphorylation increased significantly compared with control hearts. Furthermore, the TAB-induced cardiac hypertrophy was much less prominent in transgenic mice overexpressing an NCX1 mutant having defective phosphorylation sites. These data suggest that the phosphorylation status of NCX1 may play an important role in the pathogenesis of load-induced cardiac hypertrophy.
蛋白激酶Cα依赖性钠/钙交换蛋白1（NCX1）的磷酸化和钙调神经磷酸酶活性都是慢性去氧肾上腺素（PE）处理的肥厚性新生大鼠心肌细胞中观察到的NCX活性降低所必需的。在本研究中，我们探讨了体内肥厚是否会发生相同变化的可能性。在胸主动脉缩窄（TAB）小鼠的肥厚心脏中，与对照心脏相比，NCX1磷酸化显著增加。此外，在过表达具有缺陷磷酸化位点的NCX1突变体的转基因小鼠中，TAB诱导的心脏肥大明显不那么突出。这些数据表明，NCX1的磷酸化状态可能在负荷诱导的心脏肥大的发病机制中起重要作用。
