Word R A, Stull J T, Casey M L, Kamm K E
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9032.
J Clin Invest. 1993 Jul;92(1):29-37. doi: 10.1172/JCI116564.
Smooth muscle contraction is initiated primarily by an increase in intracellular Ca2+, Ca(2+)-dependent activation of myosin light chain kinase, and phosphorylation of myosin light chain. In this investigation, we identified pregnancy-associated alterations in myosin light chain phosphorylation, force of contraction, and content of contractile proteins in human myometrium. Steady-state levels of myosin light chain phosphorylation and contractile stress were correlated positively in both tissues, but the myometrial strips from pregnant women developed more stress at any given level of myosin light chain phosphorylation. During spontaneous contractions and during conditions that favor maximal generation of stress, the rate and extent of myosin light chain phosphorylation were attenuated in myometrial strips from pregnant women. The content of myosin and actin per milligram of protein and per tissue cross-sectional area was similar between myometrium of nonpregnant and pregnant women. Although cell size was significantly increased in tissues obtained from pregnant women, the amounts of contractile proteins per cellular cross-sectional area were similar. In addition, myosin light chain kinase and phosphatase activities were similar in the two tissues. The content of caldesmon was significantly increased in myometrium of pregnant women, whereas that of calponin (a smooth muscle-specific protein associated with the thin filaments) was not different. We conclude that adaptations of human myometrium during pregnancy include (a) cellular mechanisms that preclude the development of high levels of myosin light chain phosphorylation during contraction and (b) an increase in the stress generating capacity for any given level of myosin light chain phosphorylation.
平滑肌收缩主要由细胞内Ca2+增加、肌球蛋白轻链激酶的Ca(2+)依赖性激活以及肌球蛋白轻链磷酸化引发。在本研究中，我们确定了人子宫肌层中与妊娠相关的肌球蛋白轻链磷酸化、收缩力和收缩蛋白含量的改变。在两种组织中，肌球蛋白轻链磷酸化的稳态水平与收缩应激均呈正相关，但在任何给定的肌球蛋白轻链磷酸化水平下，孕妇的子宫肌条产生的应激更大。在自发收缩期间以及在有利于最大应激产生的条件下，孕妇子宫肌条中肌球蛋白轻链磷酸化的速率和程度减弱。非孕妇和孕妇子宫肌层中每毫克蛋白质和每组织横截面积的肌球蛋白和肌动蛋白含量相似。尽管从孕妇获得的组织中细胞大小显著增加，但每细胞横截面积的收缩蛋白量相似。此外，两种组织中的肌球蛋白轻链激酶和磷酸酶活性相似。孕妇子宫肌层中钙调蛋白的含量显著增加，而钙结合蛋白（一种与细肌丝相关的平滑肌特异性蛋白）的含量没有差异。我们得出结论，妊娠期间人子宫肌层的适应性变化包括：(a) 在收缩过程中阻止高水平肌球蛋白轻链磷酸化发展的细胞机制；(b) 在任何给定的肌球蛋白轻链磷酸化水平下，应激产生能力的增加。
