Age-related differences in apoptosis with disuse atrophy in soleus muscle
Age-related differences in apoptosis with disuse atrophy in soleus muscle
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DOI：
10.1152/ajpregu.00576.2004
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发表时间：
2005-05-01
影响因子：
2.8
通讯作者：
Dupont-Versteegden, EE
中科院分区：
文献类型：
--
作者：
Leeuwenburgh, C;Gurley, CM;Dupont-Versteegden, EE
肌肉萎缩与肌纤维核的损失有关，最有可能是通过细胞凋亡。我们研究了年轻（6 个月）和老年（32 个月）雄性 Fischer 344 x Brown 挪威大鼠比目鱼肌细胞凋亡程度与年龄相关的差异，这些大鼠受到 14 天后肢悬吊 (HS) 诱导的急性废用性萎缩的影响。 HS 引起的萎缩（肌肉重量和横截面积减少）与年轻大鼠（而非老年大鼠）比目鱼肌中肌纤维核的丢失有关。这导致年轻和年老大鼠的肌核域（每个核的横截面积）显着减少，而年老动物的变化更为明显。老年对照大鼠比目鱼肌中的细胞凋亡水平（TdT 介导的 dUTP 缺口末端标记和 DNA 片段化）高于年轻动物。在年轻和老年大鼠中，HS 水平显着增加，其中老年动物的变化最大。比目鱼肌中的Caspase-3活性随着年龄的增长而增加，但变化无统计学意义（P = 0.052）。然而，HS 后，年轻大鼠的 caspase-3 活性显着增加，但老年大鼠的活性却没有显着增加。免疫组织化学显示，促凋亡核酸内切酶 G（EndoG，一种线粒体特异性核酸酶）位于对照肌肉的肌膜下线粒体中，并且在年老对照动物中发生向细胞核的易位，但在年轻对照动物中则不然。年轻和年老对照大鼠的 EndoG 总蛋白含量没有差异，但 HS 后年老大鼠比年轻大鼠的比目鱼肌中 EndoG 增加了近五倍。这些结果表明，老年骨骼肌中发生肌核数量失调，并且年轻和老年肌肉中涉及细胞凋亡的途径是不同的。骨骼肌细胞凋亡部分由肌膜下线粒体通过 EndoG 易位至细胞核来介导，以响应 HS。
Muscle atrophy is associated with a loss of muscle fiber nuclei, most likely through apoptosis. We investigated age-related differences in the extent of apoptosis in soleus muscle of young (6 mo) and old (32 mo) male Fischer 344 x Brown Norway rats subjected to acute disuse atrophy induced by 14 days of hindlimb suspension (HS). HS-induced atrophy (reduction in muscle weight and cross-sectional area) was associated with loss of myofiber nuclei in soleus muscle of young, but not old, rats. This resulted in a significant decrease in the myonuclear domain (cross-sectional area per nucleus) in young and old rats, with changes being more pronounced in old animals. Levels of apoptosis (TdT-mediated dUTP nick end labeling and DNA fragmentation) were higher in soleus muscles of old control rats than young animals. Levels were significantly increased with HS in young and old rats, with the greatest changes in old animals. Caspase-3 activity in soleus muscle tended to be increased with age, but changes were not statistically significant (P = 0.052). However, with HS, caspase-3 activity significantly increased in young, but not old, rats. Immunohistochemistry showed that the proapoptotic endonuclease G (EndoG, a mitochondrion-specific nuclease) was localized in the subsarcolemmal mitochondria in control muscles, and translocation to the nucleus occurred in old, but not young, control animals. There was no difference between EndoG total protein content in young and old control rats, but EndoG increased almost fivefold in soleus muscle of old, but not young, rats after HS. These results show that deregulation of myonuclear number occurs in old skeletal muscle and that the pathways involved in apoptosis are distinct in young and old muscles. Apoptosis in skeletal muscle is partly mediated by the subsarcolemmal mitochondria through EndoG translocation to the nucleus in response to HS.