Increased ATP-ubiquitin-dependent proteolysis in skeletal muscles of tumor-bearing rats.
Increased ATP-ubiquitin-dependent proteolysis in skeletal muscles of tumor-bearing rats.
复制标题
荷瘤大鼠骨骼肌中 ATP 泛素依赖性蛋白水解作用增加。
作者：
S. Temparis;Miguel Asensi;D. Taillandier;E. Aurousseau;D. Larbaud;A. Obled;D. Béchet;Marc Ferrara;J. Estrela;D. Attaix
关于癌症恶病质中肌肉萎缩的蛋白水解途径的信息很少。在年轻大鼠中进行实验以证明小（< 0.3%体重）肿瘤是否可以激活骨骼肌中的溶酶体、Ca（2+）依赖性和/或ATP-泛素依赖性蛋白水解途径。肿瘤植入后5天，与对侧肌肉相比，吉田肉瘤附近的趾长伸肌和胫骨前肌的蛋白质质量显著降低。根据体外测量，蛋白质损失完全是由于蛋白质水解增加，而不是由于蛋白质合成抑制。溶酶体和Ca（2+）依赖性蛋白酶的抑制剂并没有减弱萎缩的趾长伸肌中蛋白水解的速率增加。因此，组织蛋白酶B和B+L活性以及组织蛋白酶B的mRNA水平未发生变化。相比之下，ATP耗竭几乎完全抑制了蛋白质分解的增加。此外，泛素，14 kDa的泛素载体蛋白E2，和C8或C9蛋白酶体亚基的mRNA水平在萎缩的肌肉中增加。肿瘤植入后12天，恶病质动物的肌肉也出现了类似的适应性变化。这些数据有力地表明，ATP-泛素依赖的蛋白水解途径的激活是主要负责在吉田肉瘤荷鼠肌肉萎缩。
Little information is available on proteolytic pathways responsible for muscle wasting in cancer cachexia. Experiments were carried out in young rats to demonstrate whether a small (< 0.3% body weight) tumor may activate the lysosomal, Ca(2+)-dependent, and/or ATP-ubiquitin-dependent proteolytic pathway(s) in skeletal muscle. Five days after tumor implantation, protein mass of extensor digitorum longus and tibialis anterior muscles close to a Yoshida sarcoma was significantly reduced compared to the contralateral muscles. According to in vitro measurements, protein loss totally resulted from increased proteolysis and not from depressed protein synthesis. Inhibitors of lysosomal and Ca(2+)-dependent proteases did not attenuate increased rates of proteolysis in the atrophying extensor digitorum longus. Accordingly, cathepsin B and B+L activities, and mRNA levels for cathepsin B were unchanged. By contrast, ATP depletion almost totally suppressed the increased protein breakdown. Furthermore, mRNA levels for ubiquitin, 14 kDa ubiquitin carrier protein E2, and the C8 or C9 proteasome subunits increased in the atrophying muscles. Similar adaptations occurred in the muscles from cachectic animals 12 days after tumor implantation. These data strongly suggest that the activation of the ATP-ubiquitin-dependent proteolytic pathway is mainly responsible for muscle atrophy in Yoshida sarcoma-bearing rats.
编码大鼠肝脏组织蛋白酶 B 前体的 cDNA 克隆的鉴定。
DOI：
10.1073/pnas.82.8.2320
发表时间：
1985
影响因子：
11.1
作者：
SanSegundo,B;Chan,SJ;Steiner,DF
通讯作者：
Steiner,DF
影响因子：
15.9
作者：
MITCH, WE;MEDINA, R;GOLDBERG, AL
通讯作者：
GOLDBERG, AL
兔网织红细胞推定泛素载体蛋白同工酶的分离和表征。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Haas,AL;Bright,PM
通讯作者：
Bright,PM