Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle
Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle
复制标题
DOI：
10.1016/j.bbrc.2015.11.019
复制
发表时间：
2015-12-25
影响因子：
3.1
通讯作者：
Deldicque, Louise
中科院分区：
文献类型：
--
作者：
Chalil, Sreeda;Pierre, Nicolas;Deldicque, Louise
合成代谢抵抗反映了骨骼肌不能通过适当刺激蛋白质合成来维持蛋白质质量。我们假设内质网（ER）应激有助于骨骼肌的合成代谢抵抗与衰老。从成年（8个月）和老年（26个月）小鼠分离肌肉并称重。对每块肌肉中的ER应激标记物进行定量，并通过使用离体肌肉模型测量比目鱼肌和EDL中S6K1的磷酸化状态来评估对亮氨酸的合成代谢反应。老化降低比目鱼肌，腓肠肌和跖肌的肌肉与体重的比例，但不是在EDL和胫骨前肌。与成年小鼠相比，ER应激标志物BiP和IRE1 α在老年小鼠的EDL中的表达更高，磷酸化eIF2 α在老年小鼠的比目鱼肌和EDL中的表达更高。S6K1对亮氨酸的反应在比目鱼肌中受损，但在EDL中没有，这表明合成代谢抵抗有助于老年小鼠比目鱼肌的体重减轻。在亮氨酸刺激之前用ER应激诱导剂衣霉素预孵育增加S6K1磷酸化超过单独亮氨酸达到的水平。由于衣霉素不损害亮氨酸诱导的S6K1反应，并基于不同的ER应激标志物调节模式，ER应激可能不参与骨骼肌衰老的合成代谢抵抗。(C)2015 Elsevier Inc. All rights reserved.
Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1 alpha was higher in EDL, and phospho-eIF2 alpha was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging. (C) 2015 Elsevier Inc. All rights reserved.