Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats.
Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats.
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DOI：
10.1152/ajpregu.00198.2005
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发表时间：
2005-10
期刊：
影响因子：
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通讯作者：
P. Siu;E. Pistilli;S. Alway
中科院分区：
文献类型：
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作者：
P. Siu;E. Pistilli;S. Alway
虽然在后肢悬吊（HS）期间细胞凋亡已被证实存在于比目鱼肌中，但细胞凋亡是否也参与了以混合纤维为主的肌肉的丧失尚不清楚。因此，我们检测了HS 14天后年轻成年和老年Fischer 344 × Brown Norway大鼠腓骨肌的凋亡反应。经HS处理后，青壮年和老年动物腓肠肌内侧肌湿重分别显著下降30%和32%，与动物体重归一化的肌肉湿重分别下降11%和15%。年轻大鼠和老年大鼠悬浮肌细胞凋亡DNA片段化程度分别增加了19%和61%。HS后年轻肌肉中Bax mRNA增加73%。在两个年龄组中，悬浮肌肉中的Bax和Bcl-2蛋白水平均高于对照肌肉。年轻大鼠和老年大鼠悬浮肌无线粒体细胞质线粒体内凋亡因子细胞色素c水平显著升高。相比之下，AIF（一种不依赖caspase的凋亡因子）的释放/积累仅在老年大鼠的悬浮肌肉中表达。我们的数据还表明，衰老通过改变Bax、Bcl-2、Apaf-1、AIF、caspases、XIAP、Smac/DIABLO和细胞色素c的含量，促进骨骼肌的促凋亡信号传导。此外，这些结果表明，细胞凋亡不仅发生在慢收缩比目鱼肌，也发生在混合纤维（主要是快纤维）腓肠肌。我们的数据与假设一致，即在HS期间，年轻成人和老年腓肠肌的凋亡信号不同。
Although apoptosis has been demonstrated in soleus during hindlimb suspension (HS), it is not known whether apoptosis is also involved in the loss of muscles dominated by mixed fibers. Therefore, we examined the apoptotic responses in gastrocnemius muscles of young adult and aged Fischer 344 x Brown Norway rats after 14 days of HS. The medial gastrocnemius muscle wet weight significantly decreased by 30 and 32%, and muscle wet weight normalized to the animal body weight decreased by 11 and 15% in young adult and aged animals, respectively, after HS. The extent of apoptotic DNA fragmentation increased by 119 and 61% in suspended muscles from young and aged rats, respectively. Bax mRNA increased by 73% in young muscles after HS. Bax and Bcl-2 protein levels were greater in suspended muscles relative to control muscles in both age groups. The level of cytosolic mitochondria-housed apoptotic factor cytochrome c was significantly increased in the mitochondria-free cytosol of suspended muscles from young and aged rats. In contrast, the release/accumulation of AIF, a caspase-independent apoptogenic factor, was exclusively expressed in the suspended muscles from aged rats. Our data also show that aging favors the proapoptotic signaling in skeletal muscle by altering the contents of Bax, Bcl-2, Apaf-1, AIF, caspases, XIAP, Smac/DIABLO, and cytochrome c. Furthermore, these results indicate that apoptosis occurs not only in slow-twitch soleus muscle but also in the mixed-fiber (predominately fast fibered) gastrocnemius muscle. Our data are consistent with the hypothesis that apoptotic signaling differs in young adult and aged gastrocnemius muscles during HS.