Oxidation enhances myofibrillar protein degradation via calpain and caspase-3.
Oxidation enhances myofibrillar protein degradation via calpain and caspase-3.
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DOI：
10.1016/j.freeradbiomed.2010.06.025
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发表时间：
2010-10-15
影响因子：
7.4
通讯作者：
Powers, Scott K.
中科院分区：
文献类型：
--
作者：
Smuder, Ashley J.;Kavazis, Andreas N.;Hudson, Matthew B.;Nelson, W. Bradley;Powers, Scott K.
关键词：
在长时间骨骼肌不活动期间，氧化应激与蛋白水解和肌纤维萎缩的加速速率有关。然而，将氧化应激与肌肉蛋白质降解联系起来的机制仍不清楚。氧化剂和肌纤维中加速的蛋白水解之间的潜在联系是肌原纤维蛋白的氧化修饰可能增强其对蛋白水解加工的敏感性。在这方面，已确定蛋白质氧化促进20 S蛋白酶体对蛋白质的识别和降解。然而，尚不清楚肌原纤维蛋白的氧化是否会增加钙蛋白酶和/或半胱天冬酶-3对其的识别和降解。因此，我们测试的假设，即氧化修饰的肌原纤维蛋白增加其敏感性钙蛋白酶和半胱天冬酶-3降解。为了验证这一假设，从大鼠骨骼肌中分离肌原纤维蛋白，并将其暴露于体外氧化以产生不同水平的蛋白质修饰。然后将修饰的蛋白质与活性钙蛋白酶I、钙蛋白酶II或半胱天冬酶-3单独孵育，并通过肽图谱评估蛋白质降解速率。我们的研究结果表明，增加蛋白质氧化的结果在逐步升级的肌原纤维蛋白的降解钙蛋白酶I，钙蛋白酶II，和半胱天冬酶-3。这些发现提供了一个机制的联系，连接氧化应激与加速肌原纤维蛋白水解在废用性肌肉萎缩。
Oxidative stress has been linked to accelerated rates of proteolysis and muscle fiber atrophy during periods of prolonged skeletal muscle inactivity. However, the mechanism(s) that link oxidative stress to muscle protein degradation remain unclear. A potential connection between oxidants and accelerated proteolysis in muscle fibers is that oxidative modification of myofibrillar proteins may enhance their susceptibility to proteolytic processing. In this regard, it is established that protein oxidation promotes protein recognition and degradation by the 20S proteasome. However, it is unknown if oxidation of myofibrillar proteins increases their recognition and degradation by calpain(s) and/or caspase-3. Therefore, we tested the hypothesis that oxidative modification of myofibrillar proteins increases their susceptibility to degradation by both calpain and caspase-3. To test this postulate, myofibrillar proteins were isolated from rat skeletal muscle and exposed to in vitro oxidation to produce varying levels of protein modification. Modified proteins were then independently incubated with active calpain I, calpain II, or caspase-3 and the rates of protein degradation were assessed via peptide mapping. Our results reveal that increased protein oxidation results in a stepwise escalation in the degradation of myofibrillar proteins by calpain I, calpain II, and caspase-3. These findings provide a mechanistic link to connect oxidative stress with accelerated myofibrillar proteolysis during disuse muscle atrophy.
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DOI：
10.1164/rccm.200202-088oc
发表时间：
2002-11-15
影响因子：
24.7
作者：
Shanely, RA;Zergeroglu, MA;Powers, SK
通讯作者：
Powers, SK
影响因子：
3.3
作者：
Whidden, Melissa A.;McClung, Joseph M.;Powers, Scott K.
通讯作者：
Powers, Scott K.
DOI：
10.1097/00005768-199712000-00005
发表时间：
1997-12-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Powers, SK;Demirel, HA;Prezant, D
通讯作者：
Prezant, D
影响因子：
5.5
作者：
Neti, Girija;Novak, Stefanie M.;Goll, Darrel E.
通讯作者：
Goll, Darrel E.
影响因子：
7.4
作者：
Kavazis, Andreas N.;Talbert, Erin E.;Smuder, Ashley J.;Hudson, Matthew B.;Nelson, W. Bradley;Powers, Scott K.
通讯作者：
Powers, Scott K.