衰老与心脏收缩异常有关,但这些收缩缺陷的病因尚不清楚。我们假设心脏收缩和调节蛋白的表达在衰老过程中发生了变化。为了调查这种可能性,左心室(LV)裂解物从年轻(6个月)和老年(24个月)Fischer344大鼠制备。SERCA2表达或磷蛋白磷酸化没有年龄相关的变化。此外,肌动蛋白同工型表达和磷酸化均无差异。然而,在衰老过程中,肌球蛋白重链(MyHC)的β亚型表达以及TnI和MyBP-C的磷酸化显着增加。在乳头状肌的透化条带中,力和Ca2+敏感性在老化过程中降低,与β-MyHC表达和TnI磷酸化的增加一致。然而,衰老过程中MyBP-C磷酸化的增加可能是一种补偿年龄相关收缩缺陷的机制.在负载Fura-2的分离心肌细胞中,Ca2+瞬变的峰值减少,但Ca2+瞬变的动力学没有改变。此外,缩短的程度以及肌节缩短和重新延长的速率均降低。这些结果表明,衰老与收缩和调节蛋白表达和磷酸化的变化有关,影响心肌的机械性能。
Aging is associated with cardiac contractile abnormalities, but the etiology of these contractile deficits is unclear. We hypothesized that cardiac contractile and regulatory protein expression is altered during aging. To investigate this possibility, left ventricular (LV) lysates were prepared from young (6 months) and old (24 months) Fischer344 rats. There are no age-related changes in SERCA2 expression or phospholamban phosphorylation. Additionally, neither titin isoform expression nor phosphorylation differed. However, there is a significant increase in β-isoform of the myosin heavy chain (MyHC) expression and phosphorylation of TnI and MyBP-C during aging. In permeabilized strips of papillary muscle, force and Ca2+ sensitivity are reduced during aging, consistent with the increase in β-MyHC expression and TnI phosphorylation. However, the increase in MyBP-C phosphorylation during aging may represent a mechanism to compensate for age-related contractile deficits. In isolated cardiomyocytes loaded with Fura-2, the peak of the Ca2+ transient is reduced, but the kinetics of the Ca2+ transient are not altered. Furthermore, the extent of shortening and the rates of both sarcomere shortening and re-lengthening are reduced. These results demonstrate that aging is associated with changes in contractile and regulatory protein expression and phosphorylation, which affect the mechanical properties of cardiac muscle.