Löfgren Mia, Fagher Katarina, Wede Oskar Karlsson, Arner Anders
Department of Physiological Sciences, Lund University, Tornavägen 10, BMC F11, Sweden.
J Physiol. 2002 Nov 1;544(3):707-14. doi: 10.1113/jphysiol.2002.027060.
The aims of this study were to investigate whether hypertrophy of the small intestinal smooth muscle leads to alterations of myosin isoform composition and shortening velocity and whether possible changes correlate with a change in the sensitivity to ADP of shortening velocity in this tissue. A partial occlusion was introduced in the distal part of the ileum of guinea-pigs. After 2 weeks, the part of the small intestine just proximal of the stenosis was hypertrophied (indicated by a significantly increased cross-sectional area). The most proximal part of the small intestine was used as control, thus enabling comparisons between hypertrophic and normal tissue from the same animal. The outer longitudinal layer of the intestinal wall was gently peeled off and used for biochemistry, RT-PCR and mechanical experiments. The desmin/actin ratio was significantly increased following hypertrophy, although myosin and actin expression were similar in control and hypertrophic tissue. In hypertrophic tissue, the myosin heavy chain mRNA with a 21 base pair insert decreased significantly. The composition of the mRNA encoding the myosin essential light chains changed towards more of the basic type (LC17b). No change in the expression of non-muscle myosin heavy chains A and B was detected. The maximal shortening velocity (V(max)) of maximally activated skinned preparations was significantly lower in the hypertrophic tissue (~50 % of control). The sensitivity of V(max) to ADP was increased in the hypertrophic smooth muscle tissue. We conclude that myosin expression is altered following intestinal hypertrophy and that these alterations affect reactions in the cross-bridge interaction, leading to a slower and more economical contractile function.
本研究的目的是调查小肠平滑肌肥大是否会导致肌球蛋白同工型组成和缩短速度的改变，以及这些可能的变化是否与该组织中缩短速度对ADP敏感性的变化相关。在豚鼠回肠远端进行部分结扎。2周后，狭窄近端的小肠部分出现肥大（表现为横截面积显著增加）。小肠最近端部分用作对照，从而能够对同一动物的肥大组织和正常组织进行比较。轻轻剥去肠壁的外纵肌层，用于生化、逆转录聚合酶链反应（RT-PCR）和力学实验。肥大后结蛋白/肌动蛋白比值显著增加，尽管对照组织和肥大组织中的肌球蛋白和肌动蛋白表达相似。在肥大组织中，带有21个碱基对插入片段的肌球蛋白重链mRNA显著减少。编码肌球蛋白必需轻链的mRNA组成向更多的碱性类型（LC17b）转变。未检测到非肌肉型肌球蛋白重链A和B的表达变化。在肥大组织中，最大激活的去表皮制剂的最大缩短速度（V(max)）显著降低（约为对照的50%）。肥大平滑肌组织中V(max)对ADP的敏感性增加。我们得出结论，肠道肥大后肌球蛋白表达发生改变，这些改变影响横桥相互作用中的反应，导致收缩功能变慢且更经济。
