Nakamura K, Ohyanagi M, Shibuya J, Yamamoto J, Iwasaki T
First Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
J Recept Signal Transduct Res. 1996 May-Jul;16(3-4):225-42. doi: 10.3109/10799899609039950.
To clarify the role of the guanine nucleotide binding proteins (G-proteins) in the pathogenesis of myocardial hypertrophy, we investigated the alterations in myocardial G proteins in 20-week-old F1b hamsters with pressure overload induced for 3 days (3-day AS), 7 days (7-day AS) and 14 days (14-day AS) by the stenosis of the abdominal aorta, and in 4- and 20 week-old BIO 14.6 Syrian hamsters (4-wk and 20-wk BIO) with genetic myocardial hypertrophy. The hearts of 7-day AS, 14-day AS and 20-wk BIO with left ventricular hypertrophy exhibited a decrease in the mRNA levels detected by Northern blot analysis and protein levels of G protein detected by Western blot analysis as compared with sham-operated and age-matched F1b hearts. The function of Gs or Gi showed a concomitant reduction in both models of myocardial hypertrophy. The hearts of 3-day AS and 4-wk BIO without myocardial hypertrophy showed no changes in G proteins as compared with sham-operated and age-matched F1b hearts. These results suggest that a decrease in G proteins is not involved in the pathogenesis of myocardial hypertrophy, but that myocardial hypertrophy reduced the G proteins.
为阐明鸟嘌呤核苷酸结合蛋白(G蛋白)在心肌肥大发病机制中的作用,我们研究了20周龄F1b仓鼠在腹主动脉缩窄诱导3天(3天主动脉缩窄,3-day AS)、7天(7天主动脉缩窄,7-day AS)和14天(14天主动脉缩窄,14-day AS)的压力超负荷情况下,以及4周龄和20周龄患有遗传性心肌肥大的BIO 14.6叙利亚仓鼠(4周龄和20周龄BIO,4-wk and 20-wk BIO)心肌G蛋白的变化。与假手术组和年龄匹配的F1b仓鼠心脏相比,7天主动脉缩窄、14天主动脉缩窄和20周龄BIO伴有左心室肥大的心脏,经Northern印迹分析检测的mRNA水平和经Western印迹分析检测的G蛋白水平均降低。在两种心肌肥大模型中,Gs或Gi的功能均随之降低。与假手术组和年龄匹配的F1b仓鼠心脏相比,3天主动脉缩窄和4周龄BIO无心肌肥大的心脏G蛋白无变化。这些结果表明,G蛋白减少并不参与心肌肥大的发病机制,而是心肌肥大导致了G蛋白减少。