SENSITIVITY AND PROTEIN-TURNOVER RESPONSE TO GLUCOCORTICOIDS ARE DIFFERENT IN SKELETAL-MUSCLE FROM ADULT AND OLD RATS - LACK OF REGULATION OF THE UBIQUITIN-PROTEASOME PROTEOLYTIC PATHWAY IN AGING
SENSITIVITY AND PROTEIN-TURNOVER RESPONSE TO GLUCOCORTICOIDS ARE DIFFERENT IN SKELETAL-MUSCLE FROM ADULT AND OLD RATS - LACK OF REGULATION OF THE UBIQUITIN-PROTEASOME PROTEOLYTIC PATHWAY IN AGING
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DOI：
10.1172/jci118264
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发表时间：
1995-11-01
影响因子：
15.9
通讯作者：
GRIZARD, J
中科院分区：
文献类型：
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作者：
DARDEVET, D;SORNET, C;GRIZARD, J
我们研究了成年人糖皮质激素诱导的肌肉萎缩和随后的恢复（7月龄）和老年人（22月龄）大鼠，由于各种疾病状态的发病率增加可能导致衰老中糖皮质激素分泌过多，成年和老年大鼠在饮用水中接受地塞米松，然后允许恢复，老年大鼠肌肉萎缩发生更快，肌肉质量的恢复受损，提示糖皮质激素可能与随着年龄增长出现的肌肉萎缩有关。根据对孵育的上滑车肌的测量，地塞米松诱导的肌肉萎缩主要是由于成年大鼠蛋白质分解增加，而老年动物蛋白质合成减少。在地塞米松处理的成年和老年大鼠的肌肉中观察到组织蛋白酶D、m-钙蛋白酶和泛素表达增加。糖皮质激素对衰老中蛋白质分解的刺激作用的消失沿着类固醇增强14-kD遍在蛋白载体蛋白E2表达的能力的丧失，其参与蛋白质底物泛素化，并且是20 S蛋白酶体（降解泛素缀合物的26 S蛋白酶体的蛋白水解核心）的亚基。因此，如果糖皮质激素在衰老中观察到的进行性肌肉萎缩中发挥任何作用，这不太可能是由泛素-蛋白酶体蛋白水解途径的激活引起的。
We studied glucocorticoid-induced muscle wasting and subsequent recovery in adult (7-mo-old) and old (22-mo-old) rats, since the increased incidence of various disease states may result in glucocorticoids hypersecretion in aging, Adult and old rats received dexamethasone in their drinking water and were then allowed to recover, Muscle wasting occurred more rapidly in old rats and the recovery of muscle mass was impaired, suggesting that glucocorticoids may be involved in the emergence of muscle atrophy with advancing age. According to measurements in incubated epitrochlearis muscles, dexamethasone-induced muscle wasting mainly resulted from increased protein breakdown in the adult, but from depressed protein synthesis in the aged animal, Increased expression of cathepsin D, m-calpain, and ubiquitin was observed in the muscles from both dexamethasone-treated adult and old rats, By contrast, the disappearance of the stimulatory effect of glucocorticoids on protein breakdown in aging occurred along with a loss of ability of steroids to enhance the expression of the 14-kD ubiquitin carrier protein E2, which is involved in protein substrates ubiquitinylation, and of subunits of the 20 S proteasome (the proteolytic core of the 26 S proteasome that degrades ubiquitin conjugates). Thus, if glucocorticoids play any role in the progressive muscle atrophy seen in aging, this is unlikely to result from an activation of the ubiquitin-proteasome proteolytic pathway.