Kayalar C, Wong W T, Hendrickson L
Molecular Biology Institute, University of California, Los Angeles 90024-1570.
J Cell Biochem. 1990 Nov;44(3):137-51. doi: 10.1002/jcb.240440303.
Upon reduction of serum in their media, mouse BC3H1 muscle cells withdraw from the cell cycle and begin to differentiate. In differentiating cells, the induction of muscle-specific genes is accompanied by a distinct morphological chance. However, differentiated BC3H1 cells do not fuse with each other; they remain mononucleated. Metalloendoprotease inhibitors selectively block the differentiation of BC3H1 cells while inhibitors of other protease types are ineffective. In these cells, the degradation of the internalized insulin is initiated by a 110 kDa, non-lysosomal protease known as the insulin-degrading enzyme. The same metalloendoprotease inhibitors that block BC3H1 differentiation also inhibit, with a similar specificity and potency, the in vitro and the in vivo degradation of insulin by the insulin-degrading enzyme. When the serum in the medium is reduced, the activity of the insulin-degrading enzyme in the cell cytoplasm increases rapidly. This increase precedes any detectable change in the differentiation state of these cells by about 12 hours. These results, together with very similar ones obtained with primary rat skeletal muscle cells, support our earlier proposal that the insulin-degrading enzyme is the metalloendoprotease involved in the initiation of the morphological and biochemical differentiation of muscle cells in culture.
当培养基中的血清减少时，小鼠BC3H1肌肉细胞退出细胞周期并开始分化。在分化细胞中，肌肉特异性基因的诱导伴随着明显的形态变化。然而，分化的BC3H1细胞不会相互融合；它们保持单核状态。金属内蛋白酶抑制剂选择性地阻断BC3H1细胞的分化，而其他类型蛋白酶的抑制剂则无效。在这些细胞中，内化胰岛素的降解由一种110 kDa的非溶酶体蛋白酶启动，该蛋白酶被称为胰岛素降解酶。阻断BC3H1分化的相同金属内蛋白酶抑制剂也以相似的特异性和效力抑制胰岛素降解酶在体外和体内对胰岛素的降解。当培养基中的血清减少时，细胞质中胰岛素降解酶的活性迅速增加。这种增加比这些细胞分化状态的任何可检测变化提前约12小时。这些结果，连同用原代大鼠骨骼肌细胞获得的非常相似的结果，支持了我们早期的提议，即胰岛素降解酶是参与培养中肌肉细胞形态和生化分化起始的金属内蛋白酶。
