Altered Myosin Isozyme Patterns from Pressure‐ Overloaded and Thyrotoxic Hypertrophied Rabbit Hearts
Altered Myosin Isozyme Patterns from Pressure‐ Overloaded and Thyrotoxic Hypertrophied Rabbit Hearts
复制标题
压力超载和甲状腺毒性肥大兔心脏改变的肌球蛋白同工酶模式
作者：
R. Litten;B. J. Martin;R. Low;N. Alpert
压力超负荷引起的心肌肥厚导致肌力发育速度、缩短速度、张力依赖的热产生和肌球蛋白ATPase活性降低，而甲状腺激素引起的心肌肥厚导致这些参数的增加。这些变化部分归因于肌球蛋白的结构变化。本研究观察了压力超负荷心肌肥厚和甲亢性心肌肥厚时肌球蛋白同工酶相对含量的变化及同工酶一级结构的差异。在正常心脏的焦磷酸盐聚丙烯酰胺凝胶中观察到三种肌球蛋白同工酶(V1=最快，V2=中间，V3=最慢的流动性)，其中V3组分占主导地位。在压力过载模型中，V1和V2成分消失或数量减少，留下V3更占优势。最显着的区别是甲亢心脏产生的同工酶谱，其中V1成为主要成分，V2和V3为次要成分。α-胰凝乳酶消化肌球蛋白重链产生了每个动物模型特有的、可重现的多肽模式，对14C-碘乙酰胺标记的肌球蛋白SHI肽的α-胰凝乳酶消化的荧光分析也是如此。我们的结果表明，肌球蛋白同工酶比例的改变可能是心脏功能改变的原因。
Cardiac hypertrophy, induced by pressure overload, leads to a depression in the rate of force development, velocity of shortening, tension-dependent heat generation, and myosin ATPase activity, whereas cardiac hypertrophy, induced by thyroxine administration, leads to an increase in these parameters. These changes have been attributed, in part, to structural changes in myosin. In this study, we have investigated changes in the relative content of myosin isozymes and differences in primary structure of the isozymes in pressure-overloaded and thyrotoxic cardiac hypertrophy in the rabbit. Three myosin isozymic forms (V1 = fastest, V2 = intermediate, V3 = slowest mobility) were observed in pyrophosphate polyacrylamide gels from normal hearts with the V3 component being the predominant species. In the pressure-overloaded model, the V1 and V2components disappeared or were present in reduced amounts leaving the V3 more predominant. The most striking difference was the isozymic profile produced in thyrotoxic hearts where the V1 became the predominant component and V2 and V3 the minor components. α-Chymotryptic digestion of myosin heavy chains produced characteristic, reproducible peptide patterns for each of the animal models, as did fluorographic analyses of a-chymotryptic digests of 14C-iodoacetamide (IAA)-labeled SHi peptides of myosin. Our results suggest that altered proportions of myosin isozymes may be responsible for altered cardiac performance.