Increased muscle proteolysis after local trauma mainly reflects macrophage-associated lysosomal proteolysis
Increased muscle proteolysis after local trauma mainly reflects macrophage-associated lysosomal proteolysis
复制标题
DOI：
10.1152/ajpendo.00345.2001
复制
发表时间：
2002-02-01
影响因子：
5.1
通讯作者：
Baracos, VE
中科院分区：
文献类型：
--
作者：
Farges, MC;Balcerzak, D;Baracos, VE
大鼠腓肠肌在创伤性损伤后48 h表现出增加的蛋白质降解（+75-115%）。损伤的肌肉显示组织蛋白酶B活性（+327%）和编码组织蛋白酶B（+670%）、组织蛋白酶L（+298%）、组织蛋白酶H（+159%）和组织蛋白酶C（+268%）的mRNA增加。在原位杂交中，组织蛋白酶B mRNA定位于损伤肌肉中的单核细胞浸润，并且在损伤组织或未损伤肌肉中的肌细胞上仅观察到背景水平的杂交。免疫金/电镜显示组织蛋白酶B仅在损伤肌肉中浸润的单核细胞的溶酶体样结构中特异性染色。肌细胞免疫细胞化学染色均为阴性。基质金属蛋白酶9（粒细胞-巨噬细胞明胶酶）的mRNA和活性不存在于未受伤的肌肉，但表达创伤后。有没有激活的ATP-泛素-蛋白酶体依赖性蛋白水解途径在受伤的肌肉，相反，不同形式的肌肉萎缩，该系统的活性和基因编码的泛素和蛋白酶体元件的表达上升。这些结果表明，肌肉细胞的蛋白水解系统在局部损伤后保持不受刺激，并且炎性浸润细胞的溶酶体酶可能是与局部创伤相关的蛋白质分解的主要参与者。
Rat gastrocnemius showed increased protein degradation (+75-115%) at 48 h after traumatic injury. Injured muscle showed increased cathepsin B activity (+327%) and mRNA encoding cathepsin B (+670%), cathepsin L (+298%), cathepsin H (+159%), and cathepsin C (+268%). In in situ hybridization, cathepsin B mRNA localized to the mononuclear cell infiltrate in injured muscle, and only background levels of hybridization were observed either over muscle cells in injured tissue or in uninjured muscle. Immunogold/electron microscopy showed specific staining for cathepsin B only in lysosome-like structures in cells of the mononuclear cell infiltrate in injured muscle. Muscle cells were uniformly negative in the immunocytochemistry. Matrix metalloproteinase-9 (granulocyte-macrophage gelatinase) mRNA and activity were not present in uninjured muscle but were expressed after trauma. There was no activation of the ATP-ubiquitin-proteasome-dependent proteolytic pathway in injured muscle, by contrast to diverse forms of muscle wasting where the activity of this system and the expression of genes encoding ubiquitin and proteasome elements rise. These results suggest that proteolytic systems of the muscle cells remain unstimulated after local injury and that lysosomal enzymes of the inflammatory infiltrated cells are likely to be the major participant in protein catabolism associated with local trauma.