Mechanisms of the suppressing effects of BDM on the actomyosin interaction ; as an experimental model of the muscle fatigue

BDM 对肌动球蛋白相互作用的抑制作用机制；

• 批准号: 09670077
• 负责人: UMAZUME Yoshiki
• 金额: $ 0.45万
• 依托单位: The Jikei University School of Medicine, Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670077/
• 关键词: Skeletal Muscle; BDM; Fatigue; X-ray diffraction; 筋原線維

We investigated the molecular mechanisms of the inhibiting effects of BDM (2, 3-butanedione monoxime) on the actomyosin interaction and compared them with the properties of actomyosin during the skeletal muscle fatigue. Using a strong synchrotron radiation source, the effects of BDM on the molecular structure of myosin and actin in the living and skinned skeletal muscle fibres. In the resting states, BDM significantly increased the resting equatorial intensity ratio. Also BDM suppressed the Ca ion activated contraction, whereas the equatorial intensity ratio was close to the value in normal contraction. BDM also reduced the intensity increase of the meridional actin layer lines and intensity decrease of the second myosin meridional during activation indicating that BDM suppresses the skeletal muscle contraction by mainly inhibiting actomyosin interaction. It has a smaller effect on the equatorial reflections and myosin layer-lines than on the actin layer lines, suggesting that BDM-influenced myosin heads may bind to actin without following the symmetry of the actin helix. We also studied the effects of BDM on the skeletal myofibrils shortening. BDM has little effects on the unloaded shortening, but clearly slowed the loaded shortening. These effects of BDM seems similar to the properties of fatigue skeletal muscles, and indicates BDM treated muscles to be a good experimental model of skeletal muscle fatigue.

我们研究了BDM（2，3-丁二酮单肟）抑制肌动球蛋白相互作用的分子机制，并与骨骼肌疲劳过程中肌动球蛋白的性质进行了比较。利用强同步辐射光源，研究了BDM对活体和去皮骨骼肌纤维中肌球蛋白和肌动蛋白分子结构的影响。在静息状态下，BDM显著增加静息赤道强度比。此外，BDM抑制钙离子激活的收缩，而赤道强度比接近正常收缩的值。BDM还可降低激活过程中肌动蛋白层线的强度增加和第二肌球蛋白肌动蛋白层线的强度降低，表明BDM主要通过抑制肌动球蛋白相互作用来抑制骨骼肌收缩。它对赤道反射和肌球蛋白层线的影响比对肌动蛋白层线的影响小，这表明BDM影响的肌球蛋白头可能与肌动蛋白结合，而不遵循肌动蛋白螺旋的对称性。我们还研究了BDM对骨骼肌肌原纤维缩短的影响。BDM对无负荷缩短影响不大，但明显减缓负荷缩短。BDM的这些作用与疲劳骨骼肌的性质相似，表明BDM处理的肌肉是一种良好的骨骼肌疲劳实验模型。