INDUCED ADAPTATIONS IN MYOSIN PHENOTYPE AND MUSCLE MASS

这一建议的主要假设是肌肉肌球蛋白的变化 重链(MHC)表型由不同于 导致肌肉肥大。一系列的实验将检验 不同类型重抗力训练范式在训练中的作用 MHC表型可塑性的调节与补偿性生长 (肥大)骨骼肌纤维。这些范例将包括 等长收缩、偏心收缩和同心收缩，这将是 以不同的强度和持续时间应用。我们将检验这一假设 需要慢速跨桥自行车运动的收缩范例 诱导较慢的MHC(主要是I型和IIa型)的上调； 然而，收缩范例需要接近最大缩短 速度或功率输出会导致这些MHC的下调。我们 假设这些转换是通过改变表达来调节的 与甲状腺相关的因子(受体和辅助蛋白) 荷尔蒙作用。相反，我们认为肌肉质量的改变 (肌纤维横截面积)是由大小和累加引起的 施加在肌肉上的力的大小与跨桥自行车无关 运动学。我们认为肥厚性改变在一定程度上是由 胰岛素样生长因子-1的自分泌/旁分泌效应 包括通过训练肌肉增加IGF-1的表达，从而 引发一系列导致蛋白质积累的事件。这个 拟议的实验将分为两个阶段，每个阶段 多个阶段。在第一阶段，第一阶段将审查 在等轴测和偏心过程中改变张力-时间积分 收缩在介导FAST-MHC表达上调中的作用 肌肉抽搐。此阶段的第二阶段将确定是否同心 收缩最大限度地缩短肌肉向下的速度 调节反重力肌肉中I型MHC的表达。第二阶段将 确定不同的力量产生模式如何改变肌肉质量 结合IGF-1的表达。总而言之，这些实验将 更清楚地定义特定机械因素的作用和 相应的亚细胞因子在MHC表型调控中的作用 肌肉发达。

The primary hypothesis of this proposal is that changes in muscle myosin heavy chain (MHC) phenotype are mediated by processes distinct from those leading to muscle hypertrophy. A sequence of experiments will examine the role of different types of heavy resistance training paradigms in the regulation of MHC phenotype plasticity and the compensatory growth (hypertrophy) of skeletal muscle fibers. These paradigms will consist of isometric, eccentric, and concentric types of contraction, which will be applied with varying intensity and duration. We will test the hypothesis that contraction paradigms requiring slow cross bridge cycling kinetics induce up regulation of slower MHCs (chiefly type I and type IIa); whereas, contraction paradigms requiring either near maximal shortening velocities or power output induce down regulation of these same MHCs. We postulate that these transformations are mediated via altered expression of factors (receptors and auxiliary proteins) associated with thyroid hormone action. In contrast, we propose that alterations in muscle mass (myofiber cross sectional area) result from the magnitude and accumulated amount of force imposed on the muscle independent of cross bridge cycling kinetics. We propose that hypertrophic changes are mediated, in part, by an autocrine/paracrine effect of insulin-like growth factor (IGF-1) involving increased IGF-1 expression by trained muscles, thereby initiating a cascade of events leading to protein accumulation. The proposed experiments will be broken down into two phases each with multiple stages. In Phase I the first stage will examine the role of varying the tension-time integral during both isometric and eccentric contractions in mediating up regulation of type I MHC expression in fast- twitch muscle. Stage II of this phase will determine if concentric contractions maximizing the shortening velocity of the muscle down regulate type I MHC expression in antigravity muscle. Phase II will ascertain how paradigms varying force production alter muscle mass in conjunction with IGF-1 expression. Collectively, these experiments will more clearly define the role of specific mechanical factors and the corresponding subcellular factors in the regulation of MHC phenotype and muscle mass.